In the proposed studies which are to be funded for 5 years are aimed at the further development and characterization of polioviruses as vectors for HIV and SIV antigens to make them more genetically stable, less pathogenic, and more efficient carriers of foreign antigens. These new vectors will be based on the Sabin vaccines. Recombinant viruses will be constructed without using cloning methods, a novel approach developed in the first funding cycle of this work. Work will also be aimed at optimizing the insertion of relevant SIV and HIV antigens into these vectors concentrating on Env, Gag, Nef and potential CTL inducers (pol, Tat, Rev, etc). The development of transgenic mice susceptible to Sabin I replication will add to the more efficient and less expensive evaluation of the genetic constructs. The Third part of this proposal is to evaluate the ability of these vector vaccines to produce functional cellular activity against the vector and the foreign proteins. Finally, as an extension of previous work, the use of these vectors in immunization protocols of susceptible monkeys to evaluate and optimize the route, dose, and scheduling of immunization to achieve good mucosal responses in the genital and GI tract.
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| Lidsky, Peter V; Andino, Raul; Rouzine, Igor M (2017) Variability in viral pathogenesis: modeling the dynamic of acute and persistent infections. Curr Opin Virol 23:120-124 |
| Menéndez-Arias, Luis; Andino, Raul (2017) Viral polymerases. Virus Res 234:1-3 |
| Whitfield, Zachary J; Dolan, Patrick T; Kunitomi, Mark et al. (2017) The Diversity, Structure, and Function of Heritable Adaptive Immunity Sequences in the Aedes aegypti Genome. Curr Biol 27:3511-3519.e7 |
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