The flu vaccine is a public health tool designed to protect individuals from influenza viruses. It works by preparing the immune system to recognize and fight off the flu, thereby reducing the risk of illness and its potential complications. Creating this vaccine each year involves a detailed scientific and manufacturing process.
Selecting the Right Strains
Influenza viruses are constantly changing due to antigenic drift, small mutations in their surface proteins. This necessitates a new flu vaccine annually to remain effective against circulating strains. Global health organizations, such as the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC), play a central role in monitoring flu activity worldwide.
Scientists at WHO collaborating and national influenza centers analyze thousands of flu virus samples globally. Twice a year, typically in February for the Northern Hemisphere and September for the Southern Hemisphere, experts review this data. They then recommend specific influenza virus strains, usually two A strains and one or two B strains for quadrivalent vaccines, that are predicted to be most prevalent in the upcoming flu season. This selection process occurs many months in advance to provide manufacturers sufficient time for vaccine production.
The Production Process
Once the specific influenza strains are selected, vaccine manufacturers begin the process of mass production. There are three primary methods approved for flu vaccine production: egg-based, cell-based, and recombinant. Each method involves distinct steps to generate the vaccine antigens.
The most traditional method, used for over 70 years, is egg-based production. It begins with injecting candidate vaccine viruses into fertilized chicken eggs. The eggs are then incubated for several days, allowing the viruses to replicate within the egg’s fluid. After incubation, the virus-containing fluid is harvested. For inactivated vaccines, these viruses are then killed, and the viral antigen, primarily hemagglutinin (HA), is purified and formulated into the vaccine.
Cell-based production uses cultured mammalian cells, such as Madin-Darby Canine Kidney (MDCK) cells, instead of eggs. In this method, candidate vaccine viruses are inoculated into these cultured cells and allowed to replicate for several days. The virus-containing fluid is collected, and the viral antigen purified. Advantages of cell-based production include potentially faster manufacturing and less reliance on the supply of chicken eggs. This method also avoids potential viral adaptations that can occur when viruses are grown in eggs, which could otherwise affect vaccine effectiveness.
Recombinant production, the most recently developed method, utilizes genetic engineering. It does not require flu viruses, eggs, or animal cells. Scientists identify the gene for the hemagglutinin (HA) protein, the antigen that triggers an immune response. This HA gene is combined with a baculovirus, a virus infecting invertebrates.
The recombinant baculovirus delivers genetic instructions into insect cells, typically fall armyworm cells, which rapidly produce large quantities of HA antigen. This antigen is harvested, purified, and used to formulate the vaccine. Recombinant technology significantly shortens the production timeline compared to traditional methods.
Ensuring Safety and Efficacy
After the flu vaccine is produced, it undergoes rigorous testing and regulatory oversight to ensure safety and efficacy before public distribution. Extensive quality control measures apply to every vaccine batch.
Manufacturers conduct purity and potency testing to confirm the vaccine contains the correct amount of active ingredient and is free from contaminants. Sterility testing is also performed to check for any bacterial or fungal contamination. For new vaccines or significant changes, safety testing involves clinical trials, which typically proceed through three phases. Phase I trials involve a small group to assess safety and immune responses, followed by Phase II with a larger, diverse group to further evaluate safety and immune responses. Phase III trials involve thousands of participants to confirm effectiveness and identify rare side effects.
Government agencies, such as the U.S. Food and Drug Administration (FDA), play a role in regulatory approval. Manufacturers submit applications, including all safety and effectiveness data, to the FDA for review. The FDA inspects manufacturing facilities and evaluates data before approving each vaccine batch for release. Post-market surveillance continues once the vaccine is in use, allowing ongoing monitoring of its safety and effectiveness.