8th Conference on Retroviruses and Opportunistic Infections


Chicago, IL - February 4 - 8, 2001




Efficient containment of a highly pathogenic immunodeficiency virus challenge by DNA priming and recombinant MVA boosting

Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:50 (abstract no. 24)

H. Robinson1, R. Amara1, B. Moss2, H. McClure1, and J. McNicholl3
1Yerkes Regional Primate Res. Ctr. and Emory Univ. Sch. of Med., Atlanta, GA; 2NIAID, NIH, Bethesda, MD; and 3CDC, Atlanta, GA.


BACKGROUND: A vaccine consisting of DNA priming and recombinant modified vaccinia virus Ankara (rMVA) booster immunizations has contained a highly pathogenic immunodeficiency virus challenge administered by a mucosal route. Two SHIV-89.6 DNA immunizations followed by a single rMVA booster have raised high frequencies of multi-epitope anti-viral T cells in rhesus macaques with diverse histocompatibility types.

METHODS: The SHIV-89.6P challenge virus was administered intrarectally at 6 months after the booster immunization, a time when vaccine responses were in memory.

RESULTS: The challenge virus infected all of the vaccine as well as the control animals. However, in the vaccine groups, all of the animals were protected against the loss of CD4 cells, and in the three most successful groups (primed intradermally or intramuscularly with 2.5 mg of DNA or intradermally with 250 µg of DNA), 15 out of 18 animals had levels of plasma viral RNA at or below the level of detection (1000 copies of viral RNA per ml of plasma). Such low levels are associated with long term non-progression and lack of transmission in HIV infected humans. In contrast, all of the non-vaccinated controls underwent a "crash" in CD4 cells and had very high steady state viral RNA levels, approximately 100 times higher than in typical HIV-1 infected humans. An inverse correlation between the frequencies of vaccine-raised T cells and the copies of viral RNA in plasma (p<0.01) suggested that protection had been mediated by cellular immunity.

CONCLUSION: Our results provide hope that DNA priming and rMVA booster immunizations will be an effective vaccine strategy for stemming the continuing advance of the AIDS epidemic.

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.