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.