Influenza

Influenza virus is a globally important respiratory pathogen which is associated with a high degree of morbidity and mortality annually. The rapid evolution of influenza A and B viruses contributes to the annual seasonal epidemics (localized outbreaks) in humans as well as occasional pandemic (worldwide) outbreaks. Despite improvements in development of antiviral therapies during the last decade, vaccination remains the most effective method of prophylaxis. For those at risk of developing complications from influenza infection, annual vaccination is recommended as it induces a good degree of protection and is generally well tolerated by the recipient. Currently there are two types of influenza vaccines in use, the live-attenuated vaccine (LAV) given intranasally/orally, and the inactivated vaccine (IV) delivered subcutaneously or intramuscularly. The available trivalent IV (TIV) elicits good serum antibody responses but induces poor mucosal IgA antibody and cell-mediated immunity. In comparison, the LAV elicits a more complete (humoral and cellular) immune response, similar to the type of immune response produced in the development of natural immunity to a specific strain. IV and LAV vaccines for seasonal influenza are effective in preventing and curbing the spread of influenza-related disease, but new technologies such as reverse genetics, production of recombinant proteins and use of cell culture to manufacture vaccine stocks could be used to improve the production of seasonal vaccines and to develop pandemic vaccines in the future. These new methods of virus production should help to develop vaccines that would be safe, cross-protective against variant influenza strains, require less virus per dose than current vaccines, and take less time to prepare the large amounts of virus necessary for vaccine production. Furthermore, pandemic vaccines against highly virulent strains, such as the H5N1 virus, can be generated much faster using reverse genetics approaches. Other technological breakthroughs such as production of vaccines that promote the induction of innate immune responses by signaling through Toll-like receptors or the use of adjuvants that boost the immunogenicity of current vaccine formulations would decrease the amount of antigen required to promote a response in recipients. Finally, development of “universal influenza virus vaccines,” which target conserved components of the virus that are not subject to change, would allow us to produce both seasonal and pandemic vaccines that would be protective against more strains than the strains circulating in any given year.