Influenza viruses are highly infectious RNA viruses that cause epidemic respiratory disease in the human population. There is an urgent unmet need for an influenza vaccine with greater potency, durability of antibody response, and strain-cross reactivity that can be developed more rapidly than conventional influenza virus. The recent epidemic spread of H1N1 and H5N1 viruses underscores the need to design vaccines that are more effective against new strains. Influenza vaccines developed using the existing model are susceptible to failure since significant HA and NA antigenic variation can occur in the time that elapses from selection of the vaccine candidate strain and virus exposure. Vaccine that have built-in cross-subtype efficacy could prevent significant spread of an emerging or re-emerging strain. A universal vaccine would have to spur an immune system attack on part of the influenza virus that does not vary from strain to strain. A cross-subtype vaccine containing immunogenic consensus sequence epitopes could achieve this goal, which is the focus of this proposal. We hypothesize that vaccines based on defined epitopes presented by the infected cells is far superior than protein subunit or motif predicted epitopes based vaccines because free proteins processing by the immune system may be different from the same protein in the viral particles. The overall objective of this proposal is to develop a novel universal influenza vaccine, which encompasses cross reactive humoral and cell mediated antigenic epitopes. In this phase I proof of concept proposal, we will extend our preliminary studies to identify a panel of HLA-A2 processed and presented cross strains conserved epitopes directly from influenza virus infected cells. These T cell epitopes will be combined with B cell epitopes in a gold glyconanoparticle vaccine delivery system and characterized for influenza specific T and B cell responses. In the phase II, additional HLA supertypes specific shared epitopes will be identified and combined with the conserved B cell eptiopes for the development of a universal influenza vaccine.
Influenza viruses cause repeated infections in humans and are a significant cause of morbidity and mortality annually accounting over 36,000 deaths each winter in the United States. The recent epidemic spread of H1N1 and H5N1 viruses underscores the need to design vaccines that are more effective against new strains. Influenza vaccines developed using the existing model is susceptible to failure since significant antigenic variations exist between the strains and mutation that occur more rapidly than most other viruses. A person who develops immunity to one strain of the virus is not well protected from a different strain. There is an urgent unmet need for an influenza vaccine with greater potency, durability of antibody response, and strain- cross reactivity that can be developed more rapidly than conventional influenza virus. In this phase I program, we will identify a panel of cross strains conserved T cell epitopes from influenza virus and combine with the conserved B cell eptiopes in a gold glyconanoparticle vaccine delivery system and characterize influenza specific immune responses for the development of a universal flu vaccine that would generate long lasting cross protective T cell and antibody responses against influenza family of viruses.
| Testa, James S; Shetty, Vivekananda; Hafner, Julie et al. (2012) MHC class I-presented T cell epitopes identified by immunoproteomics analysis are targets for a cross reactive influenza-specific T cell response. PLoS One 7:e48484 |
| Testa, James S; Philip, Ramila (2012) Role of T-cell epitope-based vaccine in prophylactic and therapeutic applications. Future Virol 7:1077-1088 |
