Developing an encapsulated inactivated H1N1 influenza vaccine
The purpose of this study was to evaluate the efficacy of an alginate encapsulated formalin inactivated influenza virus vaccine in mice. Currently approved parenteral vaccines provide protection of the lower respiratory against pneumonia, a common complication of influenza virus infection. However, upper respiratory tract infections still occur, despite vaccination. Protection of the upper respiratory tract would likely be better elicited by vaccinating via a mucosal route. In this study, mice vaccinated subcutaneously with alginate encapsulated virus mounted an antigen specific systemic antibody and lymphocyte proliferative response, even following simulated gastric juice pretreatment of the vaccine. The antibodies produced in response to the encapsulated virus were shown to inhibit hemagglutination induced by influenza virus, similar to that stimulated by nonencapsulated virus. Mice vaccinated orally with encapsulated virus mounted a less vigorous immune than mice vaccinated subcutaneously, but were significantly protected against challenge with virulent H1N1 influenza virus, as compared to negative control vaccinees, as lower titers of live virus were recovered from the lungs and tracheas of vaccinated mice than the controls. Coencapsulation of the mucosal immune adjuvant cholera toxin did not enhance the response to orally administered encapsulated virus, but did increase the immunoglobulin A response to nonencapsulated virus administered orally, and increased the degree to which nonencapsulated virus vaccinees were protected against virulent challenge. While the loading efficiency of the alginate microparticles with various test antigens was shown to be enhanced by zinc ions, the immune response in mice vaccinated subcutaneously with influenza virus that was encapsulated in the presence of calcium only, 0.5% (w/v) calcium chloride with 0.05% zinc chloride, or saturated calcium chloride and zinc chloride solution mounted nearly identical immune responses. As parenterally administered encapsulated virus was shown to be immunogenic, modifications are suggested to potentially enhance the uptake of virus loaded microparticles from the intestinal tract following oral administration.