Virus Selection
The first step in making a vaccine is identifying the virus it is intended to target. In the case of influenza, there are several strains, each of which mutates frequently. According to the World Health Organization (WHO), laboratories around the world routinely collect samples of circulating influenza viruses and submit them to the WHO Collaborating Centers for Reference and Research on Influenza. Using genetic analysis, the most common strains are identified, as are common genes between strains. Every year around April, scientists make what amounts to a prediction about which strains are likely to be the most common and which will pose the greatest danger to human health when the flu season officially begins on the fortieth week of ever year. According to the Centers for Disease Control and Prevention (CDC), the seasonal flu vaccine is a "trivalent" vaccine, which means it combats three different strains: the influenza A (H3N2) virus, the regular seasonal influenza A (H1N1) virus (not the 2009 H1N1 virus) and the influenza B virus.
Preparation of the "Vaccine Virus"
B-cells of the immune system makes antibodies to molecules expressed on the surface of viruses. Therefore, a key step in making an effective flu vaccine involves combining the contents of a weak or defective strain of influenza virus with the surface markers, or "coat," of the strains predicted to cause disease that year. This hybrid is called a "vaccine virus."
According to a 2008 article in the journal "Vaccine," influenza strains naturally exchange genes in a process known as "antigenic shift." Vaccine viruses actually engineer themselves when pathogenic and non-pathogenic strains are incubated together. Usually, several new viruses emerge. Genetic analysis and sometimes tests in animals are required to identify which of the new viruses most closely resembles the disease-causing strain on the outside with only the genes of the benign strain inside the core. This process takes at least three weeks.
Quality Control
Once one or more suitable candidates have been identified for the "vaccine virus," the next step is to turn them into vaccine. Sometimes, one strain may grow faster or more reliably than another, which is an important consideration since influenza vaccine must be mass produced. According to the WHO, hen eggs are used as the standard growth medium for influenza vaccines because they are plentiful and the virus grows well inside them. Once the process has been perfected, which takes about three weeks, the "recipe" is turned over to vaccine manufacturers who will take an additional seven to 10 weeks to produce a vaccine that is suitable for either intranasal (live, attenuated) or intramuscular (killed, inactivated) administration.
Clinical Testing and Distribution
Regulatory agencies in almost all countries require clinical testing of influenza vaccine in a small number of patients to assure that the vaccine performs as expected and to identify adverse effects before large scale distribution. While approval for other kinds of drugs can take up to 10 years, the expedited testing process for flu vaccine is usually completed in as little as four weeks, according to the CDC. Once initial safety tests are complete, companies must participate in mandatory post-marketing surveillance of safety and efficacy.
References
- WHO: Pandemic influenza vaccine manufacturing process and timeline
- "Vaccine"; The Biology of Influenza Viruses; N.M. Bouvier, P. Palese; September 2008
- CDC: Selecting the Viruses in the Seasonal Influenza (Flu) Vaccine
