Identification of Virus
It takes approximately six months to make an effective flu vaccine. In every case, the first step is to identify the virus or viruses the vaccine is intended to target. This is a complicated process. According to the World Health Organization, 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. Genetic analysis is used to identify mutations among previously characterized strains and to locate new strains of influenza virus--such as the novel H1N1 virus first identified by the U.S. Centers for Disease Control and Prevention (CDC) in March 2009--as they arise. This process is continuous, although the selection of viruses for the seasonal flu vaccine begins about six months in advance of the flu season (which, according to the CDC, officially begins on the 40th week of every year).
Preparation of "Vaccine Virus"
The immune system makes antibodies to molecules expressed on the surface of viruses. Therefore, a key step in making an effective flu vaccine involves engineering a weak or defective influenza virus that exhibits the surface markers or "shell" of strains that cause disease in humans. This 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 novel re-arrangements result. Genetic analysis and sometimes tests in animals are required to identify which of the new viruses most closely resemble the disease-causing strain on the outside but contain only the genes of the benign strain on the inside. The process takes about three weeks.
Quality Control
Once one or more candidates are identified for the "vaccine virus," the next step is to try to grow them to make vaccines. Sometimes, one strain may grow faster or more reliably than another, which is an important consideration because the 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.
Mass Production
Vaccine manufacturers get the vaccine virus from WHO laboratories and mass-produce it into a form that's suitable for distribution. It may be 7 to 10 weeks before a test batch of vaccine is available for clinical testing. 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. This testing usually takes at least four weeks. Once it's completed, vaccine manufacturers in the United States are also required to participate in mandatory post-marketing surveillance to assess the safety and efficacy of the vaccine.
References
- World Health Organization Influenza Vaccine Process Overview
- Vaccine; The Biology of Influenza Viruses; N.M. Bouvier, P. Palese; September 12 2008
- Centers for Disease Control and Prevention Vaccine Q&A
