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308 Prime-Boost Vaccination for Mucosal Immune Responses of High Avidity
A. J. Ramsay*1, M. Estcourt2, I. Ramshaw2, D. Boyle3, and C. Ranasinghe1
1Ctr. for Biomolecular Vaccine Technology, Univ. of Newcastle, NSW, Australia; 2John Curtin Sch. of Med. Res., Canberra, Australia; and 3CSIRO Australian Animal Hlth. Lab., Geelong, Australia
Background: Our studies are directed primarily toward the generation of virus-specific cell- and antibody-mediated immunity in cervico-vaginal and rectal tissues. Such responses may be critical for initial control of HIV infection.
Methods: We have devised novel prime-boost strategies, using DNA vaccines and fowlpoxvirus (FPV) vectors, for induction of immune responses in genital and rectal tissues. Vaccine delivery was via combinations of intranasal and systemic routes and immune responses were analyzed by ELISA, direct CTL assay, and tetrameric/MHC complexes.
Results: We have made several novel findings. Both intranasal and epidermal delivery of DNA vaccines primed for specific antiviral CD4+ T-cell activity and IgA/IgG antibody responses in the reproductive tracts of female mice following a single intranasal boost 4 weeks later with FPV. These responses have persisted for at least 26 weeks. Analyses with tetrameric/MHC complexes ex vivo and lytic assays were used to show that antigen-specific mucosal CTL of high avidity were also generated. Strong systemic antiviral responses were also detected. Importantly, intranasal immunization with either of these vectors alone gave no evidence for such widely disseminated mucosal responses. In addition, a rectal challenge model was established in which protection was demonstrated and was associated with potent CTL and Th1 cell responses.
Conclusions: Our mucosal DNA/FPV prime-boost strategy offers exciting prospects for the generation of “high quality” mucosal (genital and rectal) and systemic immune responses and, therefore, effective vaccination against HIV/AIDS.
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