In the US, about 36,000 deaths occur each year due to influenza and its associated diseases, and 85% of these deaths are in the elderly population. Immunization with flu vaccine is considered the best way to prevent seasonal epidemics and pandemics of influenza. Currently, two different vaccines are used in the United States: 1) a killed vaccine, which has been available since 1945;and 2) a live, attenuated vaccine, approved by the FDA in 2003. The live attenuated vaccine is not approved for use in the elderly because of safety concerns. While the protection from the killed vaccine is strong in young adults, the efficacy in the elderly is limited. Therefore, it is critical to develop a new formulation of flu vccine to improve the efficacy of vaccination in the elderly. One possible method is to include adjuvants, which are known to enhance the immune response to vaccination;the current flu vaccines contain no adjuvants. Alum, the first adjuvant approved for use in the US, can significantly increase Th2-, but not Th1-, type antibody responses after immunization. However, it is not included in the current flu vaccine because it does not significantly enhance flu vaccine efficacy. A recent study has shown that although alum can enhance the Th2-type antibody response to flu vaccine, it not only fails to improve vaccine efficacy but even makes it worse as measured by more severe weight loss and significantly higher virus loads in lungs. The results of this study further suggest that a Th1-type antibody response induced by flu vaccine plays a more critical role in protection. Importantly, aging causes the immune system to shift toward a Th2-dominant state, with a corresponding reduction in the Th1 response. Therefore, it is important to find a way to enhance Th1-type responses to improve the efficacy of flu vaccination in the aged population. Recently, we found that a protein from the helminth parasite Onchocerca volvulus, named O. volvulus activation- associated secreted protein-1 (Ov-ASP-1), can significantly enhance the Th1-type response when used with flu vaccine in aged mice. Based on this data, we hypothesize that immunization with flu vaccine in the presence of recombinant Ov-ASP-1 (rOv-ASP-1) will significantly improve the efficacy of immunization and protection in the elderly. In this SBIR Phase I application, we will test the use of rOv-ASP-1 and the combination of alum and rOv-ASP-1 as adjuvants to enhance both Th1 and Th2 response in an aged mouse model toward the development of a novel formulation of flu vaccine that may overcome the shortcomings of current flu vaccine technology and significantly improve the efficacy of flu vaccination in the elderly.
Influenza is a severe infectious disease endangering the health of people: in the US alone, about 36,000 deaths occur each year due to influenza and its associated diseases, and 85% of the deaths are the elderly. While immunization with flu vaccine is considered the most effective way to prevent influenza in young adults, the efficacy in the elderly is limited. In this SBIR Phase I application, we will test the use of a protein (rOv-ASP-1) and the combination of Alum and rOv-ASP-1 as adjuvants for the development of a novel formulation of flu vaccine that may overcome the inadequacies of the current flu vaccine and significantly improve the efficacy of flu vaccination in the elderly.
|Jiang, Jiu; Fisher, Erin M; Hensley, Scott E et al. (2014) Antigen sparing and enhanced protection using a novel rOv-ASP-1 adjuvant in aqueous formulation with influenza vaccines. Vaccine 32:2696-702|