How are influenza (flu) vaccines made? Explore the different production technologies approved by the FDA, including egg-based, cell-based, and recombinant flu vaccines. Understand the manufacturing process and key considerations for each method.

Understanding the Flu Vaccine Manufacturing Landscape

The production of influenza (flu) vaccines in the United States involves three main technologies approved by the U.S. Food and Drug Administration (FDA): egg-based, cell-based, and recombinant. Each method has its own unique process, advantages, and considerations. Let’s dive into the details of how these flu vaccines are manufactured.

Egg-Based Flu Vaccine Production

Egg-based manufacturing is the most common method for producing flu vaccines. This process has been used for over 70 years and is utilized to make both inactivated (killed) vaccines, commonly known as the “flu shot,” and live attenuated (weakened) vaccines, often referred to as the “nasal spray flu vaccine.” The egg-based production process begins with the Centers for Disease Control and Prevention (CDC) or a WHO Global Influenza Surveillance and Response System partner providing private sector manufacturers with candidate vaccine viruses (CVVs) grown in eggs. These CVVs are then injected into fertilized hen’s eggs, incubated to allow the viruses to replicate, and the fluid containing the virus is harvested. For inactivated vaccines, the viruses are inactivated (killed), and the virus antigen is purified. For live attenuated vaccines, the starting CVVs are weakened viruses that undergo a different production process. The manufacturing process continues with quality testing, packaging, and distribution, with all influenza vaccines being approved by the FDA before release and shipment.

Cell-Based Flu Vaccine Production

Cell-based flu vaccine production is an alternative to the egg-based method, approved by the FDA in 2012. This process also begins with CDC-provided CVVs, but instead of using eggs, the vaccine manufacturer inoculates the CVVs into cultured mammalian cells and allows the viruses to replicate. The virus-containing fluid is then collected from the cells, and the virus antigen is purified. Cell-based technology has the potential for a faster start-up of the flu vaccine manufacturing process, as it does not require chicken eggs. Prior to the 2019-2020 season, some of the viruses used in cell-based vaccines were originally derived in eggs, but for the 2021-2022 influenza season, all four flu viruses used in the cell-based vaccine are cell-derived, making the vaccine completely egg-free.

Recombinant Flu Vaccine Production

The third flu vaccine production technology is recombinant, which was approved for use in the U.S. market in 2013. Recombinant flu vaccines do not require a candidate vaccine virus (CVV) sample to produce. Instead, they are created synthetically. The process involves obtaining the gene that contains the genetic instructions for making a surface protein called hemagglutinin (HA) found on the influenza virus. This HA protein is then produced in insect cells using recombinant DNA technology, and the purified HA protein is used to formulate the recombinant flu vaccine.

Key Considerations for Flu Vaccine Manufacturing

While all flu vaccines must meet FDA safety and effectiveness requirements, the different production methods have their own unique considerations. Egg-based manufacturing requires large numbers of chicken eggs and may take longer than other methods. Cell-based technology has the potential for faster start-up, but still relies on the availability of CVVs. Recombinant vaccines are synthetically produced, but the technology is newer and may have different supply chain considerations.

Ensuring Flu Vaccine Quality and Availability

Regardless of the production method, all commercially available flu vaccines in the United States are made by private sector manufacturers, and the FDA tests and approves all influenza vaccines prior to release and shipment. The goal is to ensure a consistent supply of safe and effective flu vaccines to protect the public during each influenza season.

Exploring the Future of Flu Vaccine Manufacturing

As the flu vaccine landscape continues to evolve, researchers and manufacturers are exploring ways to improve the production process, increase supply, and potentially develop universal flu vaccines that could provide broader and longer-lasting protection. Ongoing advancements in technology and regulatory oversight aim to strengthen the resilience and adaptability of the flu vaccine manufacturing system.

How Influenza (Flu) Vaccines Are Made

For the United States there are three different influenza vaccine production technologies approved by the U.S. Food and Drug Administration (FDA)external icon:

• egg-based flu vaccine,
• cell-based flu vaccine, and
• recombinant flu vaccine.

All commercially available flu vaccines in the United States are made by private sector manufacturers. Different manufacturers use different production technologies, but all flu vaccines meet FDA safety and effectiveness requirements. Different vaccines have different indications. See Different Types of Flu Vaccines for more information.

Egg-Based Flu Vaccines

The most common way that flu vaccines are made is using an egg-based manufacturing process

that has been used for more than 70 years. Egg-based vaccine manufacturing is used to make both inactivated (killed) vaccine (usually called the “flu shot”) and live attenuated (weakened) vaccine (usually called the “nasal spray flu vaccine”).

The egg-based production process begins with CDC or another laboratory partner in the WHO Global Influenza Surveillance and Response System providing private sector manufacturers with candidate vaccine viruses (CVVs) grown in eggs per current FDA regulatory requirements. These CVVs are then injected into fertilized hen’s eggs and incubated for several days to allow the viruses to replicate. The fluid containing virus is harvested from the eggs. For inactivated influenza vaccines (i.e., flu shots), the vaccine viruses are then inactivated (killed), and the virus antigen is purified. The manufacturing process continues with quality testing, packaging and distribution. For the nasal spray flu vaccine (i.e., the live attenuated influenza vaccine – LAIV), the starting CVVs are live, but weakened viruses that go through a different production process. FDA tests and approves all influenza vaccines prior to release and shipment.

There are several different manufacturers that use this production technology to make flu vaccines for use in the United States. This production method requires large numbers of chicken eggs to produce vaccine and may take longer than other production methods.

Cell-Based Flu Vaccines

There also is a cell-based production process for flu vaccines that was approved by FDA in 2012. Originally, this production process also began with egg-grown CVVs per FDA regulations. However, on August 31, 2016, FDA issued an approval for Seqirus, the sole FDA-approved cell-based flu vaccine manufacturer in the United States, to begin using cell-grown CVVs. Cell-based manufacturing is used to make inactivated flu vaccines (e.g., flu shots).

The process of creating cell-based flu vaccines involves several steps. First, CDC or one of its laboratory partners, use influenza viruses that have been grown in cells to make CVVs, which are then provided to a vaccine manufacturer. Next, the vaccine manufacturer inoculates the CVVs into cultured mammalian cells (instead of into eggs) and allows the CVVs to replicate (i. e., make copies) for a few days. Then, the virus-containing fluid is collected from the cells and the virus antigen is purified. The manufacturing process continues with purification and testing. Finally, FDA tests and approves the vaccines prior to release and shipment.

Cell-based flu vaccine production does not require chicken eggs because the vaccine viruses used to make vaccine are grown in animal cells. Cell-based technology also has the potential for a faster start-up of the flu vaccine manufacturing process.

While viruses used in previous seasons’ cell-based vaccine have been grown in cells, prior to the 2019-2020 season some of the viruses provided to the manufacturer had been originally derived in eggs. For the 2021-2022 influenza season, all four flu viruses used in the cell-based vaccine are cell-derived, making the vaccine completely egg-free.

For more information, see CDC’s Cell-Based Flu Vaccines webpage.

Recombinant Flu Vaccines

This is a picture of an influenza virus. The virus’ hemagglutinin (HA) surface proteins are depicted in blue. The HAs of an influenza virus are antigens. Antigens are features of the influenza virus that are recognized by the immune system and that trigger a protective immune response. Most flu vaccines are designed to trigger an immune response against the HAs of circulating influenza viruses.

There is a third production technology for flu vaccines that was approved for use in the U.S. market in 2013 and that involves using recombinant technologyexternal icon. Recombinant flu vaccines do not require having a candidate vaccine virus (CVV) sample to produce. Instead, recombinant vaccines are created synthetically. To make a recombinant vaccine, flu scientists first obtain the gene that contains the genetic instructions for making a surface protein called hemagglutinin (HA) found on influenza viruses. HA is an antigen, which is a feature of a flu virus that triggers the human immune system to create antibodies that specifically target the virus. This gene for making flu virus HA antigen is then combined with a baculovirus, a virus that infects invertebrates. This results in a “recombinant” baculovirus. The role of the baculovirus is to help transport the genetic instructions for making flu virus HA antigen into a host cell. Once the recombinant virus enters a Food and Drug Administration (FDA) qualified host cell line, it instructs the cells to rapidly produce the HA antigen. This antigen is grown in bulk, collected, purified, and then packaged as recombinant flu vaccine. These vaccines are then quality and potency tested by FDA prior to FDA approving release of the vaccine lots to the public.

This production method does not require an egg-grown vaccine virus and does not use chicken eggs at all in the production process. While there are other vaccines on the U.S. market that use similar recombinant manufacturing processes, there is only one influenza vaccine produced using recombinant technology approved by the FDA for use in the United States at this time. This production process is the fastest because it is not limited by the selection of vaccine viruses that are adapted for growth in eggs or the development of cell-based vaccine viruses.

CDC and FDA monitor the safety of all vaccines licensed in the United States, including seasonal influenza vaccines. More information about the safety of egg-based, cell-based and recombinant influenza, including adverse events, contraindications and precautions, screening, and safe vaccine administration is available at Seasonal Influenza Vaccine Safety: A Summary for Clinicians.

Influenza Vaccine Advances | CDC

What is being done to improve influenza vaccines?

For more than a decade, collaborative efforts in the United States across the federal government and the private sector have led to improved influenza vaccine technologies that have expanded vaccine supply and/or improved vaccine effectiveness.

To further support improvement of influenza vaccines, the White House issued Executive Order (EO) 13887: Modernizing Influenza Vaccines in the United States to Promote National Security and Public Health on September 19, 2019. The EO established a National Influenza Vaccine Task Force, which CDC is a member of, and calls for the modernization of influenza vaccines and vaccine manufacturing along with increased national influenza vaccination.

What are the roles of CDC and the other federal agencies working on flu vaccine improvements?

As the nation’s leading public health agency, CDC is part of a broad inter-agency government effort to improve flu vaccines. One of CDC’s primary roles in this effort is to provide recommendations for the best public health use of existing influenza vaccines. CDC also plays a leading role in conducting year-round global virologic surveillance, supporting the selection and in some cases production of viruses used in influenza vaccines. The agency also supports the development of new and better vaccines. For example, CDC’s Influenza Division is using next generation sequencing and genomic technologies to develop better flu candidate vaccine viruses (CVVs) and more CVVs that represent major and minor genetic subgroups (e. g., clades) and induce an optimal immune response in people. In addition, CDC monitors and reports on the effectiveness of existing influenza vaccines.

Much of the work to improve influenza vaccine technology over the past decade has taken place under the auspices of influenza pandemic preparedness planning, which is led by the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA)external icon. BARDAexternal icon is charged with the development and procurement of medical and non-pharmaceutical countermeasures for pandemic influenza preparedness and response, including flu vaccinesexternal icon. The CDC, the Food and Drug Administration (FDA)external icon and the National Institutes of Health (NIH)external icon are partners in this broad inter-agency government effort. FDA is the federal regulatory agency responsible for assuring the safety, effectiveness, quality, and security of drugs, vaccines and other biological products and medical devices. NIH is the nation’s medical research agency, a role which includes conducting clinical trials for vaccines.

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What advances have been made with flu vaccines in recent years?

• • CDC has established good laboratory practice (GLP) laboratories and procedures to isolate candidate vaccine viruses (CVVs) in qualified manufacturing cell lines that serve as seeds for cell-based vaccine manufacture.
  • CDC performs two-way antigenic testing of cell CVVs that is required for them to serve as a vaccine virus.
• quadrivalent (four component) flu vaccines that protect against both lineages of influenza B viruses thus offering expanded protection against circulating influenza viruses;
• the first recombinant influenza vaccines, which can be manufactured more quickly than either egg-based or cell-based vaccines and which does not require an egg-grown vaccine virus nor eggs to produce; and,
• developing live attenuated influenza vaccines (LAIV): CDC Influenza Division’s Virology, Surveillance, and Diagnostics Branch (VSDB) develops LAIV vaccines that are shared via World Health Organization (WHO) for distribution globally. VSDB recently developed methods to stabilize the vaccine to eliminate the cold chain (learn more from this published articleexternal icon).

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What is the long-term goal of efforts to improve the flu vaccine?

One long-term goal is to reduce reliance on egg-based methods of flu vaccine manufacturing and to embrace newer vaccine manufacturing technologies that can be used to more quickly respond to novel flu outbreaks and pandemics. Another long-term goal is the development of a single flu vaccine that would provide safe, effective, and long-lasting immunity (i.e., immunity lasting multiple flu seasons) against a broad spectrum of influenza viruses, both seasonal and novel. A flu vaccine with these qualities is often referred to as a “universal flu vaccine.”

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What is CDC currently doing to support development of a universal flu vaccine?

At this time, CDC is participating in a broad inter-agency partnership coordinated by BARDAexternal icon that supports the advanced development of new and better influenza vaccines. These efforts already have yielded important successes. Part of this effort is the eventual development of a “universal vaccine” that would offer better, broader and longer-lasting protection against seasonal influenza viruses as well as novel influenza viruses. This task poses an enormous scientific and programmatic challenge, but a number of government agencies and private companies already have begun work to advance development of a universal flu vaccine.

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Where can I get more information about flu vaccine research?

More information on this topic is available at:

Influenza | History of Vaccines

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Symptoms and Causative Agent

Influenza is a respiratory illness caused by influenza viruses. There are two main types of influenza viruses (A and B) but many different strains of each type. The diseases caused by these viruses are often collectively referred to simply as “the flu. ”

Illness from influenza can range from mild to very severe depending on several factors, including the viral strain, the patient’s age, and the patient’s health. Certain groups are at higher risk for serious complications from the flu.

Symptoms of the flu tend to emerge suddenly and include fever, chills, coughing, sore throat, achiness, headaches, and fatigue. Vomiting and diarrhea may also occur, but these symptoms are more common for children than for adults.

Transmission

Influenza is primarily transmitted via infected respiratory droplets – that is, by air, via coughing and sneezing. It’s important to note that some people who are infected will not experience any symptoms (this is known as an asymptomatic infection) but will still be contagious. They can infect others without ever knowing they’re infected themselves. Even patients who experience flu symptoms may be infectious as early as a day before they first feel ill, and for up to a week after.

An important note about influenza’s ability to spread is related to its frequent genetic changes. New strains of influenza viruses appear frequently, and previous infection with a different strain does not guarantee immunity against future infection. This is one reason why the antigens in the seasonal flu vaccine usually change each year—to try to protect against whichever flu strains are currently circulating. (For more information, see “Available Vaccines and Vaccination Campaigns” below.)

Treatment and Care

Generally, flu patients are encouraged to stay home and rest, both to recover and to avoid infecting others. In mild cases, treatment is limited to addressing the symptoms of the disease: over-the-counter medicines such as acetaminophen or ibuprofen may be used to reduce fever and/or relieve aches and pains, and cough medicines or drops may be used for sore throats and to reduce coughing. Drinking extra fluids may be encouraged to prevent dehydration.

For severe cases, or for individuals at high risk for complications, physicians may prescribe antiviral medication. Many circulating influenza strains have developed resistance to available antivirals, however. Vaccination remains the primary avenue for the prevention of the flu.
 

Complications

Pneumonia is the most commonly seen complication of influenza infection. Typically, it is caused by a secondary bacterial infection such as Haemophilus influenzae or Streptococcus pneumoniae. The flu can also lead to sinus and ear infections, worsen existing medical conditions such as chronic pulmonary diseases, or cause inflammation of the heart.

Although any flu patient can experience complications from the disease, certain groups are at a higher risk for flu complications than others: older individuals, young children, people with asthma, and pregnant women are some of those whose risk for complications is elevated. In a typical flu season, people 65 or older account for 90% of deaths from the flu. (Some pandemic influenzas behave quite differently than expected in this regard; in the 2009 h2N1 pandemic, almost 90% of deaths from h2N1 influenza were among people younger than 65).

Available Vaccines and Vaccination Campaigns

Because new strains of influenza appear frequently, the seasonal flu vaccine usually changes each year. Each season vaccine is generally designed to protect against three strains of influenza: two “A” strains, and one “B” strain. From start to finish—the selection of which three strains to target with the vaccine, to the production of the final product—the development process for the seasonal flu vaccine can take up to eight months.

Influenza surveillance centers around the world monitor the circulating influenza strains for trends year-round. Genetic data is collected and new mutations are identified. The World Health Organization is then responsible for selecting three strains most likely to genetically resemble strains circulating in the coming winter flu season. For the northern hemisphere winter, this decision is made in the February prior. In some cases, one of the strains used in the previous year’s vaccine may be chosen again, if that strain continues to circulate. From this point, the development and production of the vaccine can begin.

Four to five months after the three vaccine strains have been selected (in June or July), the three vaccine strains that have been developed are separately tested for purity and potency. Only after individual testing is completed are the three strains combined into a single seasonal vaccine.

In the case of a pandemic, an additional vaccine may be created to protect against a particularly virulent or widespread strain of influenza. The need for a 2009 h2N1 influenza vaccine became apparent after the strains for the seasonal flu vaccine had already been selected, so that a separate vaccine was created.

A quadrivalent inactivated influenza vaccine was licensed in the United States in 2012, and a quadrivalent live virus nasal spray vaccine was licensed in 2013. These formulations include two influenza B strains in addition to the A strains. This vaccines began to be available, along with trivalent vaccines, in the 2013-14 influenza season.

U.S. Vaccination Recommendations

Influenza vaccination was added to the U.S. childhood immunization schedule in 2004. It is recommended that children, adolescents, and adults receive the seasonal influenza vaccine each year after six months of age; the inactivated vaccine is recommended for those age six months and older. A live, attenuated vaccine is available for those more than two years old and under age 50. Additional details and recommendations are specified on the immunization schedule.

Sources

Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Influenza. Atkinson, W., Wolfe, S., Hamborsky, J., McIntyre, L., eds. 13th ed. Washington DC: Public Health Foundation, 2015. (909 KB). Accessed 01/25/2018.

CDC. Prevention and control of seasonal Influenza with vaccines. Recommendations of the Advisory Committee on Immunization Practices, 2013-24. MMWR September 20, 2013.62;RR07:1-43. Accessed 01/25/2018.

CDC. Seasonal Influenza – Key facts about Influenza (flu). Accessed 01/25/2018.

Kamps, B.S., Hoffman, C., and Preiser, W. (eds.). Influenza Report 2006. Paris: Flying Publisher, 2006. Accessed 01/25/2018.

To read PDFs, download and install Adobe Reader.

Last update 25 January 2018

History and evolution of influenza control
from the first monovalent vaccine
to universal vaccines

J Prev Med Hyg. 2016 Sep; 57(3): E115–E120.

,¹,²,³,¹ and ⁴

I. BARBERIS

¹ Department of Health Sciences (DISSAL), University of Genoa, Italy;

P. MYLES

² Division of Epidemiology and Public Health, University of Nottingham, UK.;

S.K. AULT

³ Pan American Health Organization/World Health Organization (retired), Washington, D.C., United States of America; currently Office of the Dean, School of Public Health, University of Maryland, United States of America;

N.L. BRAGAZZI

¹ Department of Health Sciences (DISSAL), University of Genoa, Italy;

M. MARTINI

⁴ Section of History of Medicine and Ethics, Department of Health Sciences (DISSAL), University of Genoa, Italy

¹ Department of Health Sciences (DISSAL), University of Genoa, Italy;

² Division of Epidemiology and Public Health, University of Nottingham, UK.;

³ Pan American Health Organization/World Health Organization (retired), Washington, D.C., United States of America; currently Office of the Dean, School of Public Health, University of Maryland, United States of America;

⁴ Section of History of Medicine and Ethics, Department of Health Sciences (DISSAL), University of Genoa, Italy

Corresponding author.Correspondence: N.L. Bragazzi, Department of Health Sciences (DISSAL), University of Genoa, via Antonio Pastore 1, 16132 Genoa, Italy – E-mail: moc.liamg@izzagarbotreborContributed by

Authors’ contribution

MM conceived and designed the overview. IB and PM performed a search of the literature and contributed to the draft of the article. SA and NLB revised critically the manuscript. MM supervised the manuscript. All authors read and approved the final version of the manuscript.

Received 2016 Jul 8; Accepted 2016 Aug 25.

© Copyright by Pacini Editore SRL, Pisa, ItalyThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License, which permits for noncommercial use, distribution, and reproduction in any digital medium, provided the original work is properly cited and is not altered in any way. For details, please refer to http://creativecommons.org/licenses/by-nc-nd/3.0/This article has been cited by other articles in PMC.

Summary

Influenza is a highly infectious airborne disease with an important epidemiological and societal burden; annual epidemics and pandemics have occurred since ancient times, causing tens of millions of deaths. A hundred years after this virus was first isolated, influenza vaccines are an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. Innovative tools, such as recombinant technologies and intra-dermal devices, are currently being investigated in order to improve the immunological response. The recurring mutations of influenza strains has prompted the recent introduction of a quadrivalent inactivated vaccine. In the near future, scientific research will strive to produce a long-lasting universal vaccine containing an antigen that will offer protection against all influenza virus strains.

Key words: Influenza, Vaccination, History of medicine

Introduction

Influenza viruses are negative-sense, single-stranded RNA viruses belonging to the Orthomyxoviridae family, together with Isavirus, Thogotovirus and Quaranjavirus. Three types of influenza viruses, namely influenza A, B and C, are capable of determining epidemics and pandemics in humans, with influenza A being the most common circulating type and causing significant illness, being most prone to antigenic shifts and the more likely type to lead to a pandemic [1, 2]. Recently, a new genus (termed influenza virus D) has been discovered in pigs and cattle with influenza-like illness syndrome in the United States [3, 4] and in Europe [5].

Influenza is a highly infectious airborne disease that affects a significant percentage of the world’s population; local annual epidemics and pandemics have occurred since ancient times, causing tens of millions of deaths [6].

The aim of this mini-review is to provide a brief overview of the history and evolution of influenza and influenza control using vaccines.

A history of influenza: from the classical
period to the nineteenth century

In 412 BC, in the “Book of Epidemics”, Hippocrates described a putative influenza-like illness syndrome called “fever of Perinthus” or “cough of Perinthus” [7]. While some scholars claim that this is probably the first historical description of influenza (a winter and a spring epidemic of an upper respiratory tract infection occurring regularly every year at Perinthus, a port-town in Marmaraereglisi, a northern part of Greece, now Turkey), others, including the notable 19th-century editor of Hippocrates, Émile Littré (1801-1881), think that a diagnosis of diphtheria would better fit the description of complications (pneumonia, fits of coughing and wheezing, angina and paralysis of soft palate and limbs). On the other hand, symptoms such as disturbed vision and night blindness suggest a combination of diseases, including deficiency syndromes (e.g. vitamin A deficiency) [8]. In the years 1173 and 1500, two other influenza outbreaks were described, though in scant detail [9-11]. The name “influenza” originated in the 15th century in Italy, from an epidemic attributed to the “influence of the stars”, which, according to Ginctrac, raged across Europe and perhaps in Asia and Africa [12].

It seems that influenza also reached the Americas. Scholars and historians debate whether influenza was already present in the New World or whether it was carried by contaminated pigs transported on ships. Some Aztec texts speak of a “pestilential catarrh” outbreak in 1450-1456 in an area now corresponding to Mexico, but these manuscripts are difficult to interpret correctly and this hypothesis seems controversial [13].

The first reliable documents regarding influenza-like illness syndrome date from 1510, when the virus spread from Africa to Europe. The first pandemic, or worldwide epidemic, occurred in 1557, though some scholars deny that it really was an outbreak of influenza. The first pandemic/ worldwide epidemic that undoubtedly fits the description of influenza appeared in 1580, beginning in Asia and Russia and spreading to Europe via Asia Minor and North-West Africa. In Rome, it caused the death of over 8,000 people, while in Spain it decimated the populations of entire cities. Subsequently, it also affected the Americas [14].

Over the centuries, other pandemics were described worldwide. From 1404 to the middle of the 19th century, 31 influenza epidemics were recorded, including eight large-scale pandemics. Subsequently, others appeared, including three in the 20^th century [14]. Some of the most notable outbreaks occurred in 1729, in 1781-1782 (a pandemic spreading from China to Russia, Europe and North America), in 1830-1833 (a pandemic which again spread from China to India, the Philippines, Indonesia, Russia, Europe and North America), in 1847-1848, and in 1898-1900 (spreading from Europe to India, Australia, and North and South America) [14].

One of the most devastating was the pandemic of “Spanish” influenza in 1918–1919, which caused an estimated 21 million deaths worldwide and was defined by Waring as “the greatest medical holocaust in history” [14, 15].

At the end of the 19th century, the etiology of this disease had yet not been well clarified; it was believed that the disease, termed “winter catarrh”, was caused by bacteria (the so-called bacterial hypothesis), such as pneumococcus, streptococcus or Haemophilus influenzae. This latter was also named Bacillus influenzae or Pfeiffer’s bacillus, after Richard Pfeiffer (1858-1945), who described it during the 1889-1892 influenza epidemic. This bacillus had already been discovered by the Polish microbiologist Bujwid Odo Feliks Kazimierz (1857- 1942) in biopsy material a year earlier [16].

In the same period, the French microbiologists Charles Nicolle (1866-1936), Charles Lébally and René Dujarric de la Rivière (1885-1969) of the Pasteur Institute showed that the flu pathogen could pass through a fine filter. However, despite their brilliant experiments, the viral hypothesis continued to be neglected until the virus was isolated [16, 17].

In 1889, some Spanish doctors believed that influenza was a variant of dengue fever, whilst others attributed influenza outbreaks to a variety of causes including cannon fire on the western front, the building of the Madrid underground, air pollution, sunspots, or the spread of the habit of smoking poor-quality tobacco [18].

The thirties: virus isolation and the first
experimental vaccines

During the 1918-1919 pandemic, some scientists began to suspect that bacteria were not the real agent of influenza disease. One of these was the scholar Richard Edwin Shope (1901-1966), who deeply investigated swine flu in 1920. However, it was only in 1932-1933 that the English scientists Wilson Smith (1897-1965), Sir Christopher Andrewes (1896-1988) and Sir Patrick Laidlaw (1881-1940), working at the Medical Research Council at Mill Hill, first isolated the influenza A virus from nasal secretions of infected patients, thereby demonstrating the intranasal human transmission of this virus [19, 20]. A few years later, the American virologist and epidemiologist Thomas Francis Junior (1900-1969) and Smith, in England, were able to transmit the virus to mice [21]. Subsequently, in 1935, Sir Frank Macfarlane Burnet (1899-1985) and Smith separately discovered that the flu virus could be grown on the chorio-allantoid membrane of embryonated hens’ eggs [22], and in 1936 the first neutralized antibodies generated by infection by human influenza virus were isolated [23].

In the next five years, important developments took place: the demonstration that the virus inactivated by formalin was immunogenic in humans, purification of the virus by means of high-speed centrifugation, and the discovery that the influenza virus grew easily in fertilized hen eggs, a procedure that is still used today to manufacture most influenza vaccines [23].

The first clinical trials of influenza vaccines were conducted in the mid-1930s [24, 25].

A study by Smith, Andrewes and Stuart-Harris was conducted among military forces in England in 1937 using a subcutaneous vaccination with an inactivated strain isolated from a mouse lung [25].

In 1938, Francis, together with Jonas Edward Salk (1914-1995), managed to protect USA military forces. Salk would subsequently use this successful experience to develop an effective polio vaccine in 1952 [26, 27].

The forties: inactivated influenza
vaccines

Influenza vaccination had two main objectives: (i) to protect against disease, and (ii) to achieve a high vaccination rate in order to ensure protection in unvaccinated people. The first vaccine was an inactivated, monovalent preparation which only contained a subtype of the influenza A virus [26, 27].

In December 1942, large studies were begun to be conducted on the first influenza virus vaccines; these provided the first official proof that inactivated influenza vaccines could yield effective protection against flu epidemics [28].

The efficacy and safety of inactivated vaccines were first studied between 1942 and 1945; in the meantime, a new strain of flu virus was discovered, the influenza virus type B, which is the main cause of seasonal epidemics, as was the phenomenon of so-called “influenza mismatch”. Influenza mismatch is caused by major and minor mutations of circulating viruses. As a result, the virus contained in the vaccine does not match the circulating strain, determining a reduction in the effectiveness of subtype A influenza vaccines.

A new route of influenza immunization was tested in December 1942, with the subcutaneous inactivated bivalent vaccine containing viruses of type A and type B. The following years, the first bivalent vaccine was licensed in the United States and became available for use in the general population [29, 30].

The fifties: influenza mismatch
and influenza surveillance

The first system for the surveillance of circulating influenza virus strains in several countries worldwide was created in 1952 by the World Health Organization (WHO) in order to monitor the various virus mismatches reported. This important innovative tool enabled the composition of seasonal influenza vaccines to be determined on the basis of the epidemiology of influenza in the previous season [31]. In 1946, as a result of viral mutation, a new variant of influenza A (h2N1), A/FM/1/47, appeared in Australia. This gave rise to a new influenza subtype, the h3N2 strain, which caused the pandemic known as Asian flu [32].

The following year, the US Commission on Influenza recommended that a representative of this strain be included in subsequent vaccines.

The emergence of an HA subtype different from those circulating in previous seasons determined the need for pandemic influenza vaccines [31].

The sixties: split vaccines

New inactivated compounds were tested for safety and efficacy during seasonal epidemics in the 1960s, in particular two new formulations were created: split and subunit vaccines. The 1968 pandemic led to the development of trivalent inactivated vaccines (TIVs) against influenza viruses; moreover the development of new split or subunit vaccines led to a decrease of adverse reactions in children. These vaccines were split using ether and/or detergent, and haemagglutinin and neuraminidase were, in the case of subunit vaccines, purified and enriched [33].

In the same period, the first flu vaccines were licensed in Europe, while in the US annual influenza vaccination was recommended for individuals at major risk of influenza complications.

In 1968, the new virus strain h4N2 (Hong Kong) appeared, completely replacing the previous type A strain (h3N2, or Asian influenza), and led to another global pandemic with high morbidity and mortality [34]. In the same year, a new type of vaccine, the split vaccine, was authorized in the US after several clinical studies had demonstrated that it was less reactogenic than whole virus vaccines, especially in the early years of life [35].

The seventies: genetic reassortment

Split vaccines were widely used during the pandemic swine influenza in 1976 and in 1977, when the h2N1 subtype re-emerged worldwide. However, they were seen to be less immunogenic than whole virus vaccines in “primed” subjects who had never been vaccinated. Indeed, it was shown that two vaccine doses were needed in order to ensure effective protection [36].

At the beginning of the 1970s, an important innovation was introduced into the production of influenza vaccines: the genetic reassortment of influenza virus strains; this technique enabled the vaccine strains to grow faster in embryonated hen eggs [37].

The first subunit vaccine was created between 1976 and 1977. This contained only the surface antigens, hemagglutinin (HA) and neuraminidase (NA), which were isolated by means of successive purification steps.

This innovative tool proved to be highly immunogenic and well tolerated in humans, especially in children, although two doses were needed to guarantee vaccine effectiveness during epidemics [38].

The eighties: subunit vaccines

In 1980, the first subunit vaccines were licensed in the United Kingdom and are currently available in several countries worldwide.

In 1978, as a result of a major mutation, a new virus strain, h2N1, appeared on the global epidemiological scene. This strain, which was similar to a virus circulating in 1958, emerged in Russia and began to co-circulate, either simultaneously or alternately, with the previous one [39].

Antigenic drift, caused by frequent changes in the composition of the virus, determined the need to update the vaccine composition each year. This necessity prompted both the implementation of the first surveillance systems and the production of the first trivalent vaccine, which included three formulation strains (one strain of influenza A/ h2N1, an influenza virus A /h4N2 and a type B virus), in order to ensure effective protection during the 1978 pandemic.

Live attenuated influenza vaccines

In the period 1935-1941, the first clinical trials involving live attenuated influenza vaccines were conducted. The efficacy of these seasonal vaccines was guaranteed by the correspondence between the circulating strain and the strain contained in the vaccine and by the virus dose grown in hen egg embryos [34].

In 1944, Stanley described in detail the preparation and properties of an influenza virus vaccine produced in embryonated hen eggs; this vaccine was concentrated and purified by means of differential centrifugation and inactivated by means of various procedures [23].

In 1949, an important change in vaccine development involved the introduction of the use of cell cultures for virus growth.

In 1997,the so-called “avian flu” pandemic broke out in Hong Kong. This was caused by influenza virus A/ H5N1, a highly pathogenic strain.

In order to contain this pandemic, the techniques of genetic rearrangement developed in those years enabled a huge number of vaccine doses to be produced in a short time by applying recombinant DNA technology to the influenza A/H5N1 virus [34].

Recent years

In recent years, scientific research developed new techniques of immunization, which may be more immunogenic and better tolerated during administration, thereby reducing adverse events. In 2003, for instance, the FDA in the United States authorized the use of an intranasally administered live attenuated vaccine, called FluMist^®, in adults [40]. In the 2003-2004 influenza season, an outbreak in Asia was caused by an influenza A/H5N1 strain. This was later used to produce a vaccine, which was licensed in the United States by the FDA in 2007.

More recent years saw the development of adjuvanted vaccines, such as those containing alum adjuvants and the oil in water adjuvant MF-59, which significantly enhanced antigenicity [6].

Specifically, MF-59-adjuvanted vaccines were used in the elderly and in young children, and proved to elicit a good response even to pandemic strains with which subjects had not been primed by natural influenza infection. Similar responses were obtained through the use of other emulsions, such as stable emulsion (SE) and AS03, which were included in the 2009 pandemic influenza vaccines [36].

In the most recent pandemic season (2009), the influenza virus h2N1, which was transmitted to humans by pigs, was estimated to have caused more than 200,000 deaths in the first 12 months of its circulation [41].

A massive effort to produce vaccine for the new h2N1 strain began shortly after scientists identified the virus. The virus proved to grow slowly during the manufacturing process, which relies on cultivation of the virus in chicken eggs. Because of manufacturing delay, the vaccine was available in most countries after the second peak of influenza cases at the end of October leaving most people not immunized while influenza h2N1 virus was circulating [42].

In the elderly, the vaccine efficacy normally decreases, because of immunosenescence. For this reason, in 2009 the Advisory Committee on Immunization Practices (ACIP) recommended and authorized the use of high-dose Fluzone ^®, a new formulation containing a 4-fold higher HA dose than the traditional trivalent vaccine [43].

In 2011, as a result of developments in research into new vaccine delivery techniques, the FDA first authorized the intradermal administration of Fluzone^®. This new route of administration involved antigen-presenting cells (APCs) in the dermis; these cells process antigens for subsequent presentation in the lymphoid organs, resulting in the stimulation of both innate and adaptive immunity. The intradermal vaccines elicited a better immunological response than intramuscular vaccines, particularly in the elderly; in healthy adults, it yielded an immune response comparable to that elicited by the traditional vaccines, while saving on the HA dose [44-48]. In 2012, the FDA approved Fluarix^®, the first quadrivalent vaccine in the United States. This split vaccine contained two influenza A strains and two influenza B antigens. The presence of an additional influenza B strain reduced the possibility of a mismatch between the circulating viruses and the vaccine composition, while maintaining the same immunogenicity and safety as standard trivalent vaccines [49].

In 2013, the FDA approved FluBlock^®, a recombinant trivalent influenza vaccine, for use in people aged between 18 and 49 years. FluBlock^® was licensed in a spray formulation and was the first trivalent influenza vaccine made by using recombinant DNA technology. Derived from Baculovirus, it contained a 3-fold higher HA dose than traditional trivalent vaccines [50, 51]. The scale-up potential of the insect cell/baculovirus vector system may offer advantages in terms of rapid antigen change and response to a pandemic situation [31].

Currently, scientists are exploring the fascinating prospect of developing a universal vaccine by exploiting T-cells and by attempting to elicit broadly neutralizing antibodies. Moreover, efforts are being made to design M2e- or stalk-based vaccines, since these proteins (the type-2 matrix protein and the stalk domain of HA, respectively) are quite well conserved from an evolutionary standpoint [52, 53].

Conclusions

In the hundred years since the influenza virus was isolated, influenza vaccine preparations have evolved to ensure effective protection, while maintaining a good safety and tolerability profile.

The recurring mutations of influenza strains prompted the introduction of a quadrivalent inactivated vaccine, the composition of which is determined on the basis of the most frequent strains isolated in the previous season during continuous surveillance by the WHO.

Current research priorities include the development of a universal influenza vaccine that could offer protection against all influenza virus strains, thereby overcoming the challenges faced due to antigenic drift and shift or of co-circulation of different viral strains. Another important priority is to identify sustainable vaccine production platforms capable of rapidly meeting the large global demands for influenza vaccine in the face of an influenza pandemic.

ACKNOWLEDGMENTS

No funding declared for this overview. The authors thank Dr. Bernard Patrick for revising the manuscript.

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Why the Flu Vaccine Is Reformulated Every Year: East Meadow Medical P.C.: Primary Care Physicians

Welcome to National Influenza Vaccination Week, established in 2005 by the Centers for Disease Control and Prevention to promote vaccination awareness to the general public. In that spirit, Dr. Sebeen Razzaq-Ahmed and the team here at East Meadow Medical P.C. remind you to get your annual flu vaccine. You may be one of the many people we hear ask why they need to get vaccinated each year. Well, we’re here to answer that for you!

It’s no secret that influenza, commonly called the flu, is inconvenient, nasty, and downright deadly. The 2017-2018 flu season was among the worst on record, afflicting and killing more Americans — about 80,000 — than in any season dating back more than three decades. Because the flu is so common, not to mention so deadly, we always recommend that anyone who’s able to gets an updated vaccine each year.

What is the flu?

Influenza is a highly contagious respiratory illness that’s caused by the influenza virus. There are two main types of influenza virus: type A and type B. These main types are further subdivided into multiple subtypes and strains, including the well-known h2N1 strain. The effect each of these strains may have on you depends on your age and overall health.

If you have the flu, symptoms may include:

• Chills
• Fever
• Coughing
• Sneezing
• Sore throat
• Body aches
• Headaches
• Fatigue

In more extreme cases, you may experience vomiting and diarrhea. Although symptoms tend to emerge suddenly, you may find yourself experiencing a milder version in the early stages of the virus. It’s also important to note that you may be a carrier for the virus even if you aren’t experiencing any symptoms yourself.

Why do I need to get vaccinated every year?

You’ve probably noticed by now that we encourage our patients to get vaccinated each year. Why does this particular vaccine need to be administered again, even if you got a flu shot last year? It’s because new strains of the virus are constantly appearing and evolving, so the vaccine must change along with them.

Located around the world are influenza surveillance centers that annually monitor the most common strains, collecting data and identifying new and evolving strains. Once the information has been collected, the World Health Organization selects the three strains most likely to circulate during the following flu season. This decision is typically made in February, allowing the development of a new vaccine to begin around midsummer.

Because the three strains change each year, the vaccines are formulated separately before they’re combined into the final product, the trivalent vaccine. While it’s usually fairly accurate, there have been instances, such as the infamous h2N1 outbreak in 2009, that required the addition of a second, separate vaccination.

In addition to the constantly evolving strains of the flu virus, your body’s immune response changes over time. Taken together, those two factors essentially render the previous years’ vaccinations useless against new strains. This is why it’s so important to get yourself vaccinated each and every year, even if you got the vaccine last year!

When should I get vaccinated?

The flu season ranges roughly from October-March. Because the flu vaccine takes about two weeks to fully protect you from viral antibodies, we recommend you try to get vaccinated by the end of October. However, if you’ve yet to get your vaccination this year, it’s not too late!

We understand there are many questions about vaccines, especially the flu vaccine, and we always encourage our patients to ask any questions they may have. Call East Meadow Medical P.C. today to schedule your vaccination, or use the online booking tool. It’s important not just for yourself, but also for those around you!

A Universal Influenza Vaccine: How Close Are We?

This article was originally published on asm.org Aug. 23, 2019, but has since been updated by the author. 

Seasonal influenza vaccinations currently provide narrow protection against select strains of the virus.

There are now several ‘universal’ flu vaccine candidates, using a variety of technologies, in Phase 2 and Phase 3 clinical trials that aim to provide broader and longer-lasting influenza protection. While much progress has been made to develop these vaccines, researchers still have to clear several more hurdles to improve vaccine efficacy. 

Seasonal Influenza and the Need for Yearly Flu Vaccinations

There are 2 main reasons why we need seasonal influenza vaccinations:

1. Strains of influenza change annually.
2. Flu vaccine efficacy is narrow and short lived.

The flu is primarily caused by the influenza A virus (IAV), but can also be caused by the influenza B virus (IBV). Both are enveloped RNA viruses, with IAV having several different strains. A study that analyzed patient data from Glasgow, United Kingdom from 2003 to 2013 found the prevalence of IAV and IBV to be 30% and 15%, respectively, in those with respiratory illness. Both influenza virus membranes contain proteins known as hemagglutinin (HA) and neuraminidase (NA), which are important for entry and release (respectively) of the virus from infected cells. Other structural components of the virus, such as the RNA-binding matrix protein M1, the nucleoprotein (NP) that coats the viral RNA or  the ion channel M2 protein, can be recognized by our immune systems. While our immune system can mount a response to an influenza infection, it is usually specific to the strain of influenza causing infection because most neutralizing antibodies generated by either infection or vaccination target what is known as the globular head of HA. As shown in the graphic below, HA and NA are more numerous and accessible on the viral envelope and are therefore more accessible antibody targets than other components.

The viral membrane contains several membrane proteins, such as hemagglutinin (HA) and neuraminidase (NA).

Source: https://www.cdc.gov/flu/resource-center/freeresources/graphics/images.htm


The reason we need yearly flu vaccinations is partially due to changes in the sequence of the HA protein. A person exposed to 1 strain of IAV will develop neutralizing antibodies specific to the HA globular head of that strain. Random mutations in IAV make the globular head of HA highly variable over time. This process is known as antigenic drift. Antibodies that recognize a previous strain will no longer protect against the new variant. Another mechanism of evasion by the virus is known as antigenic shift, or recombination. Recombination of 2 different strains of viruses in the same infected host can yield a completely new HA that has never been seen by our immune system. Such antigenic shifts have caused pandemic strains of influenza, such as the 2009 h2N1 outbreak.  New seasonal vaccinations must be developed to provide protection against strains predicted to be common in the upcoming flu season. This is why the U.S. Centers for Disease Control and Prevention (CDC) analyzes the data on circulating strains to predict what strains to vaccinate against in the coming year. The predictive nature of vaccine design is one of the primary reasons why vaccine efficacy varies widely from year to year.

The other reason annual flu vaccination is necessary is because the antibody response to current flu vaccines is fleeting. A systemic review and meta-analysis of various influenza vaccination studies found that vaccine effectiveness waned 180 days post vaccination compared  to 15-90 days post vaccination, suggesting a fading immune response within 6 months of vaccination. Due to both variation in the virus and a temporary immune response, most influenza vaccinations have short-lived efficacy and narrow protection. Efficacy, in this scenario, refers to broad protection against multiple strains of influenza. 

Strategies for a Hemagglutinin (HA)-Based Universal Vaccine

The variability of the globular head of HA and the immune system’s preference for these epitopes has led to the search for more conserved epitopes across multiple influenza strains. If vaccines can focus the immune response against viral regions that undergo less mutation, there is a greater probability of protection on a near-universal level. Two of these strategies center on conserved regions found within HA: recombinant stalk-specific HA and chimeric recombinant HA.

The stalk, which is the domain of HA that anchors the globular head to the membrane of the virus, is relatively similar across IAV strains. This means that despite the vast number of different IAV strains, the stalk remains conserved. Conserved regions for viruses typically correspond to a preserved enzymatic activity, such as a polymerase or protease, or structural features that cannot be easily changed without deleterious effects. This is why the HA stalk is a target for universal vaccine candidates. However, recent research has highlighted the need to consider childhood and previous exposure to influenza and the ability to generate anti-stalk antibodies. The response of an individual to generating protective anti-stalk antibodies may be dependent on the influenza subtype that they were exposed to as a child.

One strategy to target the stalk involves a recombinant HA protein that lacks the globular head and contains only the stalk domain. To date, most vaccine development using this approach remains in the preclinical stage of research.

 

The second strategy for a universal vaccine uses reverse genetics to make viruses expressing recombinant, chimeric HA proteins. These constructs typically have the same stalk (the h2 clade of widely circulating IAV strains) fused with the globular head of non-human IAV strains. Sequential vaccine doses against these chimeric HAs that share the same stalk aim to generate stalk-specific antibodies that provide universal protection against IAV. Unfortunately, this approach suffers from the possibility that vaccine-generated stalk-specific antibodies may target regions inaccessible during an actual infection. Therefore, epitope mapping of the most immunogenic sites of HA stalk can help determine the availability of those sites during infection and aid in vaccine design. 

One advantage of the chimeric HA approach is that it has the potential to protect against novel pandemic IAV strains. Since non-human influenza HA globular heads are used, our immune system will generate strain-specific antibodies to the head along with the conserved stalk domain. Therefore, if a pandemic strain ever expressed that same HA, vaccinated people would be protected from an otherwise potentially lethal infection.

GlaxoSmithKline (GSK) started clinical trials of 2 different chimeric HA-based vaccines, one of which is a collaborative vaccine between GSK, Icahn School of Medicine at Mount Sinai and Duke University. This candidate completed Phase I trials in May 2020, though its fate is unknown, as it is not listed in GSK’s development pipeline. Novavax’s Nanoflu is currently in Phase 3 trials, testing the efficacy of the vaccine in an older adult population. Nanoflu utilizes a quadrivalent approach, with recombinant HA from 4 IAV strains that have been predicted to circulate during the 2019-2020 season. Nanoflu successfully demonstrated efficacy in its clinical trials, demonstrating non-inferiority against the current seasonal vaccine (which is a major hurdle for Food and Drug Administration (FDA) approval), as well as generating comparable hemagglutination assay inhibition (HAI) against the 4 influenza strains. Additionally, Nanoflu had higher seroconversion rates when compared to the seasonal influenza vaccine.

Vaxart, Inc. is currently in Phase 2 clinical trials utilizing an adenovirus vector-based vaccine expressing the HA protein of h2N1. While not strictly a universal flu vaccine candidate, the VXA-A.1 vaccine is a proof-of-concept for the use of an oral tablet-based vaccine versus the standard intramuscular injection. Recently published data from the clinical trials suggests that the vaccine was well-tolerated and provided protection against homologous h2N1. The hope is that Vaxart can establish this platform as a jumping off point for a universal influenza vaccine. 

VXA-A.1 is not the only adenovirus-vector HA influenza candidate under development. Altimmune has generated a nasal spray-administered vaccine composed of a replication-deficient adenovirus vector expressing an h2N1 HA. NasoVax completed Phase 2a clinical trials in 2019, revealing robust antibody protection against h2N1, as well as detectable increases in mucosal antibodies, suggesting induction of mucosal immunity. There is some trepidation about nasal sprays as influenza vaccine delivery systems, with evidence pointing to reduced efficacy with FluMist, an approved nasal influenza vaccine. NasoVax must clear that trepidation if it is to establish itself as an efficacious influenza vaccine.

Another promising candidate is a quadrivalent HA virus-like particle (VLP) vaccine from Medicago, Inc. This vaccine candidate completed Phase 3 trials in June 2020. This candidate is currently a proof-of-concept vaccine for the plant-based VLP technology, which uses plants to manufacture recombinant virus-like particles. These particles can be engineered to express HA proteins from influenza or spike (S) protein from coronaviruses, such as SARS-CoV-2.  If this vaccine successfully protects against seasonal flu, Medicago could repurpose the vaccine using new HA antigens. 

While many IAV researchers still believe that stalk-specific antibodies will ultimately be the most protective strategy, using this chimeric approach allows the immune system to develop antibodies against the non-human HA globular heads. Whether these will actually confer protection against novel IAV strains remains to be seen.

Recombinant M2 and Other Non-HA Vaccine Strategies

Other conserved regions in IAV include the exposed surface domain of the M2 structural protein. The M2 protein has not been a major target previously due to the lack of accessibility to antibodies. HA and NA-specific antibodies are more common than M2-specific antibodies in natural infections. 

A front runner non-HA candidate is FLU-v, a synthetic peptide-based vaccine created by Imutex. This synthetic peptide has conserved sequences for M1, M2 and NP from IAV and IBV. FLU-v completed Phase 2 trials in 2019, and has since published data on the results of the trial. Unlike most of the vaccines listed, FLU-v was designed to promote cellular (T-cell) immune responses over humoral (antibody) immunity, and demonstrated successful protection against intranasal challenge with h2N1.

Bioinformatics analysis of conserved peptides across IAV strains offers another approach. BiondVax’s M-001, created in collaboration with the National Institute of Allergy and Infectious Disease (NIAID), is a vaccine created using this method and is undergoing clinical trials. M-001 completed Phase 3 in February 2020. M-001 is a linear polypeptide with 3 repetitions of 9 conserved sequences from M1, NP and HA from IAV and IBV influenza strains. 

Osivax has a nucleoprotein nanoparticle-based vaccine known as OVX836 that has completed Phase 2 clinical trials. OVX836 induced CD4 and CD8 T-cell NP-specific responses in mice during preclinical studies, and similar results are expected from the clinical trials. Another vaccine candidate that is in Phase 2 is MVA-NP+M1, sponsored by Vaccitech. This vaccine combines NP and M1 from IAV in an adenoviral vector platform. 

Ultimately, this is not an exhaustive list of current vaccine candidates, as there are numerous ongoing Phase 1 trials and several promising pre-clinical strategies for a universal influenza vaccine. One preclinical animal study utilized an h2N1 HA stem trimer that was stabilized and formulated into capsid-like particles. They were able to show protection in mice against heterologous challenge with a different strain of IAV 28 days post vaccination. Additionally, protection against homologous h2N1 was observed 34 weeks post vaccination. Another group utilized chimeric HA composed of an H5 strain globular head and an h2 stem. The monoglycosylated chimeric HA produced stem-specific antibodies in mice. When challenged with a panel of IAV strains, they found broad protection against the tested IAV strains. 

How “Universal” Are Universal Influenza Vaccines?

While many of the above strategies protect against a variety of IAV strains and some even target IBV, researchers do not yet know how protective these vaccines will be in people. For example, dosage effects of the chimeric HA vaccines differ in mouse model experiments compared to preliminary results from human trials. Mouse models can never fully capture the immunological history of people who experience both bouts of flu and receive influenza vaccinations. Therefore, human trials are critical to test vaccine performance in people.

There is also a concern regarding the length of protection conferred by a universal vaccine. Most seasonal influenza vaccinations only provide a short-term period of efficacy. While the efficacy of several universal vaccine candidates is being assessed, it appears that many of these vaccines may also only provide short-term efficacy. Thus, instead of being a one-time replacement to the seasonal vaccine, these new strategies may only serve to replace it with a more efficacious vaccine.

It is clear that while significant progress has been made to develop a broadly protective universal vaccine, there is still more work to be done to achieve a long-term solution to influenza. While influenza continues to strike year after year, promising work on broadly effective vaccines may ultimately break our never-ending cycle of annual influenza vaccinations.

Pandemic influenza vaccine manufacturing process and timeline

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2. Preparation of the vaccine strain (called vaccine virus): The virus must first be adapted for use in manufacturing vaccine. To make the vaccine virus less dangerous and better able to grow in hen’s eggs (the production method used by most manufacturers), the virus is mixed with a standard laboratory virus strain and the two are allowed to grow together. After a while, a hybrid is formed which contains the inner components of the laboratory strain, and the outer components of the pandemic strain. It takes roughly three weeks to prepare the hybrid virus.

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3. Verification of the vaccine strain: After its preparation, the hybrid virus needs to be tested to make sure that it truly produces the outer proteins of the pandemic strain, is safe and grows in eggs. Upon completion of this process, which takes roughly another three weeks, the vaccine strain is distributed to vaccine manufacturers.

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4. Preparation of reagents to test the vaccine (with reference reagents): In parallel, WHO Collaborating Centres produce standardized substances (called reagents) that are given to all vaccine manufacturers to enable them to measure how much virus they are producing, and to ensure they are all packaging the correct dose of vaccine. This requires at least three months and often represents a bottleneck for manufacturers.

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Activities at vaccine manufacturers

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1. Optimization of virus growth conditions: The vaccine manufacturer takes the hybrid vaccine virus that it has received from the WHO laboratories, and tests different growth conditions in eggs to find the best conditions. This process requires roughly three weeks.

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2. Vaccine bulk manufacture: For most influenza vaccine production, this is performed in nine to twelve-days old fertilized hen’s eggs. The vaccine virus is injected into thousands of eggs, and the eggs are then incubated for two to three days during which time the virus multiplies. The egg white, which now contains many millions of vaccine viruses, is then harvested, and the virus is separated from the egg white. The partially pure virus is killed with chemicals. The outer proteins of the virus are then purified and the result is several hundred or thousand liters of purified virus protein that is referred to as antigen, the active ingredient in the vaccine. Producing each batch, or lot, of antigen takes approximately two weeks, and a new batch can be started every few days. The size of the batch depends on how many eggs a manufacturer can obtain, inoculate and incubate. Another factor is the yield per egg. When one batch has been produced, the process is repeated as often as needed to generate the required amount of vaccine.

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3. Quality control: This can only begin once the reagents for testing the vaccine are supplied by WHO laboratories, as described above. Each batch is tested and the sterility of bulk antigen is verified. This process takes two weeks.

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4. Vaccine filling and release: The batch of vaccine is diluted to give the desired concentration of antigen, and put into vials or syringes, and labeled. A number of these are then tested:

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• for sterility

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• to confirm the protein concentration and

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• for safety by testing in animals.

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This process takes two weeks.

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5. Clinical studies: In certain countries, each new influenza vaccine has to be tested in a few people to show that it performs as expected. This requires at least four weeks. In some countries this may not be required as many clinical trials were done with similar annual vaccine preparation, and the assumption is that the new pandemic vaccine will behave similarly.

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Activities at regulatory agencies – regulatory approval

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Before the vaccine can be sold or administered to people, regulatory approval is required. Each country has its own regulatory agency and rules. If the vaccine is made with the same processes as the seasonal influenza vaccine, and in the same manufacturing plant, this can be very rapid (one to two days). Regulatory agencies in some countries may require clinical testing before approving the vaccine, which adds to the time before the vaccine is available.

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The full process, in a best case scenario, can be completed in five to six months. Then the first final pandemic vaccine lot would be available for distribution and use.

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Key: The arrows with dotted lines preceded by non-broken arrows indicate the time period required for the first time an activity is done (non-broken arrow line) that is then repeated (dotted arrow line). The solid lines signify that the activity takes place within a finite period.

“,”datePublished”:”2009-08-06T12:30:00.0000000+00:00″,”image”:”https://www.who.int/images/default-source/fallback/icons/news.png?sfvrsn=d88eddde_0″,”publisher”:{“@type”:”Organization”,”name”:”World Health Organization: WHO”,”logo”:{“@type”:”ImageObject”,”url”:”https://www.who.int/Images/SchemaOrg/schemaOrgLogo.jpg”,”width”:250,”height”:60}},”dateModified”:”2009-08-06T12:30:00.0000000+00:00″,”mainEntityOfPage”:”https://www.who.int/news/item/06-08-2009-pandemic-influenza-vaccine-manufacturing-process-and-timeline”,”@context”:”http://schema.org”,”@type”:”NewsArticle”};

90,000 Gunzburg spoke about plans to create a unified influenza and COVID vaccine :: Society :: RBK

Photo: Win McNamee / Getty Images

The Gamaleya Center will begin clinical trials of a single influenza and coronavirus vaccine at the end of 2022.The director of the center, Alexander Gintsburg, told Izvestia about this.

According to him, a hybrid vaccine against rotaviruses was taken as the basis for a new drug, in parallel with it, a drug is being developed against various variants of coronavirus.

“The technology platform for this has already been created, but clinical trials have not yet begun. If everything goes well with this platform, it is this technology that will work, then we will move on to a more complex option – combining influenza hemagglutinin antigens and, accordingly, coronavirus S-proteins in one vaccine.The beginning of clinical trials of the new drug is the end of next year, ”Gunzburg said.

In Russia began to investigate the uniform use of vaccines against COVID and influenza

In September, the Russian Ministry of Health announced the start of studies on the simultaneous use of influenza and coronavirus vaccines.At the briefing, the head of the department, Mikhail Murashko, spoke about the beginning of preclinical studies of such a combination of drugs in animals. “Based on the results, decisions will be made on further steps,” the minister said. The Ministry of Health, in turn, said that with successful trials, a combination of influenza and COVID-19 vaccinations would help avoid overlapping diseases. “This is especially true for the autumn-winter period, when there is an increased incidence,” the ministry added.

The Deputy Minister of Health Oleg Gridnev said earlier that studies of the compatibility of influenza and coronavirus vaccines will be carried out in Russia “as soon as possible”.Prior to that, in early September, the head of the Ministry of Industry and Trade Denis Manturov said that the first results of a study of a combined Russian vaccine against coronavirus and influenza may appear by the end of 2021.

There are currently five COVID-19 vaccines registered in Russia. These are “Sputnik V” and “Sputnik Light”, created by the Moscow Center. Gamalei, “EpiVacKorona” and “EpiVacKorona-N” from the Novosibirsk center “Vector”, as well as developed at the Center. Chumakov’s drug “KoviVak”.

Over the previous day, 25,133 new cases of COVID-19 infection were detected in Russia, another 929 people died – this is a new record for daily mortality in Russia.The previous record was recorded on October 5, when 895 deaths from coronavirus were announced.

How the number of deaths from Covid-19 in Russia is changing

Daily data of the operational headquarters

Source: federal and regional headquarters for the fight against coronavirus

Data for Russia i

90,000 Preparatively: trials of a single COVID and influenza vaccine to begin in late 2022 | Articles

A technological platform for a unified influenza and coronavirus vaccine has been created in Russia.Its clinical trials will begin at the end of 2022. About this “Izvestia” said the head of the Center. N.F. Gamalei Alexander Gunzburg at a gala evening in honor of the 25th anniversary of the Russian Jewish Congress. He admitted that the vaccinated form memory cells that will maintain a higher level of antibodies. An increase in the general level of immunization will lead to the fact that it will be possible to revaccinate more than once every six months, but much less often, the scientist explained. Virologists interviewed by Izvestia clarified: 90,030 before the creation of a single vaccine, influenza and coronavirus vaccinations are not considered interchangeable; for full protection, both must be done.An interval of three weeks is required between them.

Clinical trials of a single vaccine against influenza and coronavirus will begin at the end of 2022, the director of the V.I. N.F. Gamalei Alexander Gunzburg . At the heart of the technological platform of the future drug is a hybrid vaccine against rotavirus, in parallel with it, a drug is being developed against various variants of the coronavirus.

– The technology platform for this has already been created , but clinical trials have not yet begun. If everything goes well with this platform, it is this technology that will work, then we will move on to a more complex option – combining influenza hemagglutinin antigens and, accordingly, coronavirus S-proteins in one vaccine. The beginning of clinical trials of a new drug – the end of next year , – said the expert.

Photo: Izvestia / Taras Petrenko

In addition to the Center. Gamaleas are also developing their common vaccines against influenza and coronavirus. In November 2020, the State Research Center for Virology and Biotechnology “Vector” began researching its vaccine on laboratory animals . The results of the work have not yet been reported. Vektor and Rospotrebnadzor did not provide a prompt response to Izvestia’s request.

The need to create a unified vaccination against influenza and coronavirus is due to the fact that the simultaneous infection with these diseases significantly increases the severity of the course of seasonal influenza and mortality from it , the chief researcher of the Center.N.F. Gamalei Victor Zuev. According to him, being vaccinated against only the flu or only against the coronavirus is not enough to create immunity, since these are two different viruses.

– Do not confuse sour with fresh, flu is flu, coronavirus infection has nothing to do with it. The fact is that the object of the disease is similar – the respiratory system, but these diseases, in general, are very different from each other . Coronavirus infection brings us “surprises”, especially in young people, when the central nervous system is also affected, ”the scientist said.

Therefore, he concluded, until a single vaccine against influenza and coronavirus is developed, it is necessary to be vaccinated with two different drugs.

– But between them it is necessary to observe a short break, two to three weeks , – advised the virologist.

Infectionist Evgeny Timakov explained to Izvestia that a single vaccine against influenza and coronavirus will not be worse than two separate vaccines – the amount of antibodies produced will not decrease.

– Antibodies will be produced in absolutely the same way, each vaccine will have its own, – said the expert.

According to a study by doctors at the University of Michigan, published in the American Journal of Infection Control, among those vaccinated against the flu, the proportion of those infected with coronavirus was lower than among those who did not get vaccinated against the flu.

Patients with coronavirus but previously vaccinated against influenza were less likely to need to be hospitalized and connected to a ventilator, the study said.

Photo: Izvestia / Kristina Kormilitsyna

– Now influenza vaccination increases non-specific immunity, which activates receptors responsible for antiviral work.And during vaccination against coronavirus, specific immunity is formed, therefore vaccination at the moment, before the development of a single vaccine, both are needed, ” concluded Evgeny Timakov.

On September 17, the Ministry of Health of the Russian Federation announced the start of preclinical studies of the compatibility of flu and coronavirus vaccinations. On October 4, the head of the department, Mikhail Murashko, said that “the first results are encouraging.”

On September 30, , the University of Bristol, UK, published a study showing that it is safe to be vaccinated against both COVID-19 and influenza at the same time. does not adversely affect the immune response caused by both vaccines.Both injections were given to the subjects on the same day, but in different hands.

The side effects reported by the study participants were usually mild to moderate. The tests involved three flu and COVID-19 vaccines from Pfizer and AstraZeneca.

The only competitor of the center. Gamalei and “Vector” in the development of a single vaccine against coronavirus and influenza – American Moderna. On September 9, the company announced “the first step in a new program to develop a single-dose vaccine that combines an additional dose of COVID-19 and an additional dose of influenza.”

According to a Moderna press release, the new RNA vaccine will combine the current version of the coronavirus drug and the flu shot – it is under development .

The vaccine will be a special fatty nanoparticle containing a fragment of RNA from the coronavirus. They can enter human cells and force them to produce large amounts of fragments of the SARS-COV-2 protein coat, which leads to an immune response to the pathogen COVID-19.

Head of the Department of Arboviruses and the Laboratory of Biology and Indication of Arboviruses of the Center named after N.F. Gamalei Alexander Butenko told Izvestia that the platform on which the drug Moderna is being developed differs from Russian developments.

Photo: RIA Novosti / Grigory Sysoev

– These are different platforms, they have technological differences. But the fact is that the most important thing is that there should be such antigens of viruses that contribute to the formation of antibodies and the formation of immunity in the vaccinated .Therefore, the platform and technology do not matter, it is all solvable, the main thing is to complete the task, – the expert explained.

He also emphasized that it is not uncommon to combine several vaccines in one preparation. There are combinations that include four vaccines at once against different infections, for example, for dengue fever or for different types of influenza.

Alexander Gunzburg also told Izvestia that it is necessary to revaccinate against coronavirus every six months because of the Delta strain.However, the formation of memory cells in the blood of the vaccinated is possible, as well as an increase in the level of immunization among the entire population of . Then it will be possible to vaccinate less often, the virologist emphasized.

– Mankind has remained with the “Delta” strain forever. But, perhaps, we will have continuous immunization among all vaccinated, and then revaccination will really be required much less often, – said the head of the Center. N.F. Gamalei.

Alexander Gunzburg also stated that he does not support the WHO statement that revaccination is not needed at the moment .

Earlier in an interview with Izvestia, WHO Chief Scientific Officer Sumiya Swaminatan said that the organization opposes the introduction of booster doses of the coronavirus vaccine. According to her, “the priority remains the following strategy: it is necessary that all countries of the world use their limited stocks of vaccines to ensure high coverage of the first and second doses of priority populations.”

Photo: Izvestia / Dmitry Korotaev

– WHO says this not for reasons of increasing the degree of protection of revaccinated people, but for reasons that the vaccine that is being boosted can be allowed in those countries where people have not been vaccinated at all .This is primarily about the African continent. That is, not from scientific considerations, but purely from economic and social , – stated Alexander Gintsburg.

Despite a call from WHO, some countries have made the third dose of the vaccine mandatory. In Israel, from October 3, only those who have received three vaccinations can obtain COVID passports. The certificates of those who took injections more than six months ago have been canceled. In Russia, the Ministry of Health recommends revaccinating every six months during an unfavorable epidemiological situation.In the future, the vaccination campaign can be carried out once a year.

Vaccine Development – Topics – Avian Influenza and Pandemic Threat

Vaccine development

Vaccines are the first line of defense in reducing the morbidity and mortality invariably associated with pandemics.

For a number of reasons, at the start of the pandemic and over the next few months, no country will have sufficient vaccine supplies. Large-scale commercial production of the vaccine will not begin until three to six months after the emergence of the pandemic virus.

The main capacities for the production of vaccines against the virus are concentrated mainly in Europe and North America. Today, the pace of production is clearly not keeping pace with demand, which will increase during a pandemic.

Continuous monitoring

WHO, through its network of specialized vaccine laboratories, is continuously monitoring the evolution of the H5N1 virus that has occurred since the first human infection in Hong Kong in 1997.

In these laboratories, a prototype viral vaccine strain is produced, which will be presented to specialists as a starting point for creating a vaccine. Continuous molecular analysis of viruses carried out in these laboratories helps to ensure that the work on developing a vaccine is not standing still. This is especially important in light of the virus’s ability to mutate in 2005.

Commercial vaccine production

Since a pandemic vaccine is intended to be closely related to a true pandemic virus, commercial production cannot begin before the emergence and characterization of a pandemic virus.

However, WHO recommended that professionals working on this issue and government authorities develop operational measures for licensing and marketing a pandemic vaccine, which they did.

In addition, WHO at international meetings urges the international community to find ways to increase productive capacity and provide developing countries with access to effective vaccination at an affordable cost. However, recent trends indicate that most developing countries will not have access to vaccine during the first wave of a pandemic and possibly beyond.

90,000 Experts assessed the possibility of creating a polyvaccine – Rossiyskaya Gazeta

The creation of a polyvaccine that would protect both from COVID-19 and from influenza is quite possible, said the head of the Gamaleya Research Center Alexander Gintsburg. However, many vaccine makers are working on a “super-vaccine” against a bunch of infections.

Someday we will be able to defend ourselves with one “super vaccine” – from many infections at once. Photo: REUTERS

The whole world is now concerned about the attack of the delta strain and whether it is able to break through the immune defenses after vaccination.Scientists from different countries confirm: the effectiveness of the current vaccines against “delta” is lower (although not much), so there is a question of modifying them taking into account the modified strain. The same Gamaleya Research Center has made a candidate drug based on several genetic variants of the S-protein of the coronavirus and is planning to begin clinical trials in early 2022. The next step is to expand the vaccine to protect against influenza as well.

Polivaccines have been used for a long time. Children, for example, are vaccinated against measles, whooping cough and tetanus at one time.But there are no such vaccines for respiratory infections yet. Although scientists from the Smorodintsev Institute of Influenza are already working on a combined vaccine against both infections. The head of the institute, Dmitry Lioznov, said that we are talking about an intranasal drug: the vaccine will be injected into the nose twice with an interval of two weeks. The work on the “double action” vaccine was also reported at the State Research Center “Vector”.

The creators of mRNA vaccines also have ambitious plans. Moderna and Pfizer are currently working on booster vaccines for COVID-19.In the United States, it was officially announced that starting September 20, all Americans will receive the right to take the third dose eight months after the first vaccination. At the same time, Moderna is also working on polyvaccines for many infections. The company has begun or is planning human trials of vaccines against 10 viruses.

The head of the company, Stephen Bansell, said that mRNA technology is well suited for creating a wide variety of vaccines: against new and rare infections, such as Nipah and Zika viruses, and for old and “not amenable” for vaccine protection, such as HIV.And these were not empty words: in July, Moderna began testing the latest flu vaccine. And a few days ago, according to Bloomberg, clinical trials of a candidate drug against HIV started.

“In the long term, the company aims to develop an annual ‘supervaccine’ that could suppress many respiratory infections, including COVID, influenza, and others. Our goal is to provide multiple mRNAs at a time during the annual vaccination in August or September,” explained Bansel.

At the same time, some experts consider such ambitions excessive. The fact is that updating vaccines requires huge investments, and the cost of drugs will eventually rise. At the same time, for example, the current vaccines protect against all new strains of the “corona”, albeit with a slight decrease in effectiveness.

“While several companies are looking into updated vaccines, this update may not be needed yet,” Bloomberg quoted Ramon Lorenzo-Redondo, a molecular virologist at Northwestern University in the United States, as quoted by Bloomberg.While there is no clear evidence of loss of protection, updating vaccines every time a new variant is distributed around the world may not be the best strategy, the expert said. “If we were to update the vaccine with every major change in the viral population, we would enter an endless process that would be ineffective due to the logistics and testing required to approve each new vaccine,” says Dr. Redondo. the data will ever show a significant loss of vaccine effectiveness, updating it will be a necessary step. “

How relevant is the “race” for the supervaccine, “RG” commented Alexei Paramonov, head of the Rassvet clinic, which conducts clinical trials of tests and vaccines against COVID-19. “Coronavirus infection continues to be studied, and we have been using vaccines against it quite recently, it is quite logical, having developed a modified version against delta, to evaluate its effectiveness in comparison with the basic version,” the expert said. I would not make a complete analogy with the flu.The flu virus is much more complex than the coronavirus, and its mutation capacity is much higher. We have been living with coronavirus for more than a year and a half, and so far there are not so many significant mutations that would critically change its properties. Of course, there will be changes in vaccines, as is the case with many other infections. But I would refrain from saying that we will need a new vaccine against COVID-19 every year, like with the flu. Moreover, if we still manage to vaccinate a large proportion of the population, the circulation of the coronavirus will fade away and, accordingly, it will mutate less. “

Russian immunologist – on influenza vaccination during the COVID-19 pandemic – RT in Russian

Influenza vaccine will not protect against coronavirus, but it can stimulate immunity. This was stated in an interview with RT by the head of the Laboratory for Vaccine Prevention and Immunotherapy of Allergic Diseases of the Research Institute of Vaccines and Serums. I.I. Mechnikov Russian Academy of Medical Sciences Mikhail Kostinov. He also noted that regular vaccinations, in particular against the flu, can have the effect of trained immunity.

– Recently, medRxiv published a study by scientists from the Netherlands who reported that an annual flu shot can provide cross-protection against COVID-19.Has this kind of research been conducted before, and can a flu shot really protect against coronavirus?

– The flu shot does not protect against coronavirus, but it does activate certain innate immunity receptors that remain in the body for a long time. When they meet the SARS-CoV-2 virus, these receptors quickly recognize it, and a cascade of reactions is immediately triggered. The earlier the immune response begins, the faster antibodies are formed that protect a person from the virus.That is, the influenza vaccine has a nonspecific immune response, which ultimately affects the tolerance of coronavirus infection, namely, the favorable outcome of the disease.

Even after vaccination against influenza, for several months, other cells – dendritic cells – are activated, which determine protection against all infectious pathology. It can be influenza or coronavirus, or other infections. In addition, the flu vaccine also activates special immune response functions that reduce inflammation in the body.This is where the complex effect of the influenza vaccine against the SARS-CoV-2 virus comes from.

Studies of the last year in practice show that those previously vaccinated against seasonal flu, if they become infected with coronavirus, are less in hospitals, less likely to need oxygen therapy and mechanical ventilation. Most importantly, the risk of death is reduced.

– Should you get the flu shot after getting the COVID-19 vaccine? Are there risks of possible side effects?

– Yes, you need to be vaccinated.There will be no side effects. There are even recommendations not only Russian, but also international. He was vaccinated against coronavirus infection – in a month it will be possible to get a flu vaccine, and vice versa. Even those who have had the coronavirus can get the flu vaccine.

• RIA News
• © Pavel Lisitsyn

– Are antibodies against coronavirus also produced after the flu shot?

– No.The flu vaccine only forms antibodies against the flu. What is associated with the coronavirus is the so-called non-specific effect of the vaccine, because the specific one implies protection against the flu specifically. And the nonspecific effect appears due to the activation of immunity, which prepares a person to meet any viruses and bacteria, including coronavirus.

Also on the topic

“We do not expect serious side effects”: Director of the Institute of Immunology – on the drug for the treatment of coronavirus “MIR 19”

In Russia, the second stage of clinical trials of the drug for the treatment of coronavirus “MIR 19” is coming to an end.About this in an interview with RT …

– According to scientists from the Netherlands, if you constantly get vaccinated against influenza, there is an effect of trained immunity, which allows you not to get infected with other viruses, including COVID -19. Is it really so?

– The effect of trained immunity can be caused not only by the influenza vaccine, but also by the measles vaccine. Vaccines for pneumococcus, diphtheria, tetanus, for example, are also powerful immunomodulators.Therefore, any vaccine trains the immune response.

– Is there a danger of contracting new strains of coronavirus after a flu shot with a weakened immune system?

– No. The vaccine does not reduce immunity, but stimulates it. Those who do not vaccinate against any infections have a chance to get infected.

– Will universal vaccinations be created in Russia and in the world that can protect against both viruses – influenza and coronavirus?

– There are already preclinical studies in Russia, where they are trying to combine two vaccines at once.Such developments are underway because viruses are from the same group. Until a common vaccine is developed that uses a single syringe, it is likely that coronavirus and influenza vaccinations will be given on the same day.

Vaccination campaign against influenza in the Admiralteysky District

Dear residents of the Admiralteisky district!

A vaccination campaign against influenza was launched in the Admiralteisky District on 20 August.For the period until November 1, a unified work schedule for vaccination rooms has been established on weekdays: from 8.00 to 14.00 and from 15.00 to 20.00 with technical breaks.

Every resident of our area can get a flu shot at a convenient time at a polyclinic at the place of residence at a convenient time:
• SPb GBUZ “City Polyclinic No. 24” at the address: nab. Bypass channel, 140
• Children’s department of St. Petersburg GBUZ “City polyclinic №24” at the address: nab. Bypass channel, 123
• SPb GBUZ “City polyclinic number 27” at the address: Voznesensky pr., 27
• Children’s department of St. Petersburg GBUZ “City polyclinic number 27” at the address: st. Glinka, 8
• SPb GBUZ “City Polyclinic No. 28” at Pidezdnoy Lane, 2

Flu vaccine can be life-saving
The opportunity to actively study the influenza virus and its properties appeared only in 1940, when the virus began to be grown in chicken embryos. Since then, a great step forward has been made in the study of influenza – the ability to mutate has been discovered, and all regions of the virus that are capable of variability have been identified.The most important consequence of these studies was, by far, the development of an influenza vaccine.

Most people with the flu get sick for about a week and then feel better. But some, especially young children, pregnant women, the elderly, and people with chronic illnesses, can become seriously ill.
Getting the flu vaccine every year is the best way to protect yourself and your child from a serious illness. The vaccine can be given to all people from the age of 6 months.
Flu vaccines are updated annually. Both domestic and foreign vaccines include the same names of three influenza strains, selected as the most relevant for the upcoming season through observation around the world, including our country. It is known that with repeated vaccinations the effectiveness increases. This is due to the fact that the formation of antibodies (protective antiviral proteins) in previously vaccinated people occurs faster.

It is best to vaccinate in advance, before the epidemic develops – from September to December.It is also possible to vaccinate during an epidemic, but it must be borne in mind that immunity is formed within 7-15 days, during which it is best to carry out additional prophylaxis with antiviral agents.

Remember, the flu can be very serious for you, your family and friends, but you can be protected by getting vaccinated.

Annual vaccinations are the only adequate protection against influenza. Flu vaccines will protect you and your loved ones from this dangerous disease.

Get vaccinated every year and make sure your children and your parents are vaccinated too.

90,000 Prevention of influenza (memo to the public)

Prevention of influenza

(information for the public)

In autumn and at the beginning of winter, with the onset of cold weather, all of us – both children and adults – are trapped by colds or ARVI. What preventive measures and when should you take to protect yourself from influenza?

First of all – flu shot .It helps protect against the flu virus and should be taken very seriously. Currently, there are various types of vaccines, and the dosage, frequency, method of administration of the vaccine depend on many factors. The optimal time for vaccination against influenza for residents of Russia is from the end of August to November. Within a month, the body manages to develop the necessary protective antibodies and prepare for the onset of a period of increased incidence. It is not recommended to get the flu shot before August, as antibody levels begin to decline 6 months after vaccination.There are flu shots for pregnant women and nursing mothers. Currently, vaccination of pregnant women against influenza is carried out using an inactivated vaccine, starting from the second trimester of pregnancy, and this will not have any negative effect on the fetus. Influenza vaccination for a nursing mother provides additional protection for the baby, as the antibodies produced by the mother in response to the vaccine are passed into the infant’s body through breast milk.

The introduction of an inactivated virus (or its parts) into the body causes the production of different types of antibodies, which makes it possible to create a multi-level system of protection against influenza, and since influenza viruses have similar structures to SARS viruses, the anti-influenza antibodies produced after vaccination also protect the body from SARS – with an efficiency of 50-60%, the number of cases of pneumonia, exacerbations of chronic diseases is reduced.Already two weeks after vaccination, anti-influenza antibodies accumulate in the body and it becomes immune to the disease. Protective proteins recognize the virus and destroy it, preventing it from multiplying. Sufficient immune reactivity of the body lasts about 6 months (according to other sources – up to a year), which ensures its high resistance to the influenza virus throughout the epidemic season. The effectiveness of immunization with modern influenza vaccines is 70-90% and depends both on the specific vaccine, the conditions of its storage and transportation, and on the epidemiological situation at a particular time.That is, the likelihood that the vaccinated child will get sick with the flu still remains, but at the same time he will get sick with it in a mild form and without the development of complications.

From August 22, 2017, the next pre-season vaccination campaign to immunize the population against influenza will start in the Altai Territory. The campaign will run for 10 calendar weeks and should be completed by October 31, 2017.

In 2017, in the Altai Territory, the total plan of vaccinations against influenza will be 1.039 million people, including children – 209.1 thousand.people (children under 3 years old are vaccinated twice), adults – 829.79 thousand people.

According to the Ministry of Health of the Russian Federation, only the domestic vaccine SOVIGRIPP will be used, without preservatives – for children from 6 months. life, with a preservative – for adults.

In addition, in the Altai Territory, a stock of influenza vaccines is being formed in the non-state company ASKO-MED in the amount of 20,000 doses:

• Influvac (Netherlands)
• Waxigripp (France)
• Grippol-plus (Russia )

What kind of vaccine Sovigripp is

Sovigripp – what is it? This is another domestic influenza vaccine released in 2013.The manufacturer of the Sovigripp vaccine is the Russian company Microgen. The drug is completely produced at a domestic enterprise; components are not purchased from abroad.

The Sovigripp vaccine contains components of the surface envelope of influenza viruses of various strains. Each year, the vaccine differs in composition depending on the varieties of priority influenza viruses projected for that season. Influenza A and B viruses are the most common.

The goal of vaccine prevention is to create protection against influenza by introducing particles of viral cells.In addition to viral particles, adjuvants are added to influenza vaccines – substances that prolong immunity. In all vaccinations for these purposes, “Polyoxidonium” is used, but in the vaccine “Sovigripp” the adjuvant “Sovidon” was used for the first time. It has an immunomodulatory, membrane stabilizing and antioxidant effect due to which the effect of vaccination increases and the number of cases of acute respiratory infections decreases. Vaccination “Sovigripp” is effective in 80–90% of cases.