AEGiS-08CROI: Vaccination with VSV G protein exchange vectors expressing HIV env and SIV gag proteins protects rhesus macaques from challenge with highly pathogenic SHIV 89.6P.

8th Conference on Retroviruses and Opportunistic Infections

Chicago, IL - February 4 - 8, 2001

Vaccination with VSV G protein exchange vectors expressing HIV env and SIV gag proteins protects rhesus macaques from challenge with highly pathogenic SHIV 89.6P

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 23)

N. F. Rose¹, P. A. Marx^2,3, A. Luckay³, D. F. Nixon², W. J. Moretto², S. M. Donahoe², and J. K. Rose¹
¹Yale Univ. Sch. of Med., New Haven, CT; ²Aaron Diamond AIDS Res. Ctr., New York, NY; and ³Tulane Regional Primate Res. Ctr., Covington, LA.

BACKGROUND: Rhesus macaques were vaccinated and boosted with live, recombinant vesicular stomatitis virus (VSV) vectors (serotype Indiana) expressing the HIV-1 (89.6) env and SIV_mac239 gag genes.

METHODS: The boosts were performed with novel VSV vectors expressing the HIV and SIV proteins but expressing VSV G proteins from two VSV serotypes that are not neutralized by antibody to the first VSV vector or to each other.

RESULTS: There was no detectable pathogenesis associated with vaccination or boosting by oral, intramuscular, or intranasal routes. Cellular immune responses to both retroviral antigens were detected using both ELISPOT and cytokine flow cytometry assays. ELISA antibody titers to the HIV 89.6 envelope were detected after boosting and were comparable to those seen in long-term SHIV-infected monkeys. Neutralizing antibody titers to the HIV Env protein and the VSV G proteins were detected also. At two months following the last boost, the animals were challenged i.v. with SHIV89.6P, which contains the SIV_mac239 gag gene and an HIV env gene that has diverged extensively from the HIV(89.6) env gene present in the vaccine vectors. Within two weeks, CD4 positive lymphocyte counts fell to near zero in control animals and have remained there for three months. CD4 counts dropped initially in the vaccinees, but remained above 300/ml and later increased to near normal values. Viral loads in the vaccinees were detectable initially, but were undetectable or at least 100-fold below those in the unvaccinated animals at 42 days post-challenge.

CONCLUSION: VSV vectors are promising candidates for HIV vaccine development.

2001-02-04
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Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.