Advances in Flu Vaccines

All currently licensed flu vaccines in the United States are produced in chicken eggs, manufactured in a process that dates back to World War II. Fertilized eggs are injected with the influenza virus, followed by chemical inactivation, purification, and testing—a process that takes six to nine months and requires millions of chicken eggs. In addition to their protracted development, egg-based vaccines have induced hypersensitivity reactions in egg-allergic recipients and in rare cases caused debilitating disorders (A 1976 swine flu vaccine caused 500 incidences of Guillain-Barré syndrome, a paralyzing autoimmune disorder).

Scientists and public health officials from the NIH, NIAID, and FDA gathered at the NIH campus on Dec. 11 to discuss current flu vaccines and ones being developed. The theme was simple: egg-based vaccine production is slow and outdated but continues to produce safe and effective vaccines while other technologies are being developed. These alternative platforms include DNA vaccines, recombinant subunit vaccines, virus-like particle vaccines, and synthetic peptide vaccines.

To mount an immune response against an influenza virus, antibodies must be produced against a specific antigen on the virus. Two types of antigens used to characterize the influenza virus are hemagglutinin (HA) and neurominidase (NA)—hence flu virus subtypes denoted as H1N1 (“swine” flu) and H5N1 (“avian” flu).

Recombinant subunit vaccines are at the forefront of the vaccine platforms in development. With this method, a virus is used to infect insect cells to produce high amounts of a protein. This protein is then packaged as the vaccine. Carole Heilman, director of the division of microbiology and infectious disease at the NIAID, explained the protocol and why it is the most promising in new vaccine technologies: one is able to immediately identify the gene of the surface protein one wants to elicit an immune response against, transfect the DNA into a baculovirus, infect insect cells in 48 to 72 hours, and obtain a yield of approximately 90% of usable protein for use as the vaccine.

Heilman noted that the baculovirus expression system is one of the most advanced new technologies, with one five-hundred liter fermentor having the equivalent production capacity of 50,000 eggs. Protein Sciences, a pharmaceutical company using the baculovirus technology, has an influenza vaccine candidate in Phase III named FluBlok.

Research into influenza structure and immunity will provide opportunities to develop vaccines quicker and even preemptively, something that will prove necessary as forms of influenza continue to evolve and mutate almost daily. Not only will vaccine improvement support a more rapid and flexible response to influenza outbreaks, the technologies developed will also apply to prophylaxis against diseases like malaria, HIV, and tuberculosis.