View All Abstracts for Session 37
195 Rhabdovirus-Based Vectors Expressing HIV-1 Env or Gag Induce Vigorous Cellular Responses against HIV-1 and Infect Efficiently Human Dendritic Cells
J. McGettigan1, H. D. Foley1, S. Sarma1, M. Otero1, C. A. Siler1, J. Orenstein2, R. J. Pomerantz1, and M. J. Schnell*1
1Thomas Jefferson Univ., Philadelphia, PA, USA and 2George Washington Univ. Med. Ctr., Washington, DC, USA
Background: Our previous experiments with replication-competent vaccine strain-based rabies virus (RV) expressing HIV-1 envelope protein from both a laboratory-adapted HIV-1 strain (NL4-3) and a primary HIV-1 isolate (89.6) showed that RV-based vectors are excellent for B-cell priming. Here we analyze the cellular responses against HIV-1 envelope and Gag proteins expressed by RV-based vectors.
Methods: BALB/c mice received a single vaccination with different RV-based vectors expressing HIV-1 gp160 or Gag. The cellular responses against the expressed antigens were analyzed by standard chromium release assays, FACS staining for INF-g secretion, ELISPOT assay, and tetramer staining. In addition, mature and immature human dendritic cells were isolated and used as targets for our vaccine vehicles.
Results: Our results indicate that a single inoculation of mice with RV-expressing HIV-1 gp160 induces a strong, long-lasting memory CTL response specific for HIV-1 envelope proteins. Moreover, CTLs from immunized mice were able to cross-kill target cells expressing heterologous HIV-1 envelope proteins from HIV-1 strains such as 89.6, JR-CSF, and BaL. The potency of the RV-based vectors were confirmed with a recombinant RV expressing HIV-1 Gag. A single inoculation with this vector resulted in about 30 to 40% of CD8+ T cells specific for an HIV-1 p24 epitope after challenge with a recombinant vaccinia virus expressing HIV-1 Gag. Moreover, our results indicate that RV-based vectors are highly efficient in targeting both immature and mature human dendritic cells.
Conclusions: These results further confirm and extend the potency of RV-based vectors as potential HIV-1 vaccines. Similar vectors expressing SIV Gag and Env will enable us to further study these vectors in the SIV/macaque model system.
Contact Author about this Abstract
