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.
| Dolan, Patrick T; Whitfield, Zachary J; Andino, Raul (2018) Mapping the Evolutionary Potential of RNA Viruses. Cell Host Microbe 23:435-446 |
| Lidsky, Peter V; Lukyanov, Konstantin A; Misra, Tvisha et al. (2018) A genetically encoded fluorescent probe for imaging of oxygenation gradients in living Drosophila. Development 145: |
| Xiao, Yinghong; Dolan, Patrick Timothy; Goldstein, Elizabeth Faul et al. (2017) Poliovirus intrahost evolution is required to overcome tissue-specific innate immune responses. Nat Commun 8:375 |
| 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 |
| Stern, Adi; Yeh, Ming Te; Zinger, Tal et al. (2017) The Evolutionary Pathway to Virulence of an RNA Virus. Cell 169:35-46.e19 |
| Xiao, Yinghong; Rouzine, Igor M; Bianco, Simone et al. (2017) RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence. Cell Host Microbe 22:420 |
| Tassetto, Michel; Kunitomi, Mark; Andino, Raul (2017) Circulating Immune Cells Mediate a Systemic RNAi-Based Adaptive Antiviral Response in Drosophila. Cell 169:314-325.e13 |
| Xiao, Yinghong; Rouzine, Igor M; Bianco, Simone et al. (2016) RNA Recombination Enhances Adaptability and Is Required for Virus Spread and Virulence. Cell Host Microbe 19:493-503 |
Showing the most recent 10 out of 33 publications
