Immunotherapy of Congenital SIV Infection.
Abstract
A DNA prime/protein boost vaccination trial was initiated against challenge with a chimeric simian-human immunodeficiency virus, termed SHlV-vpu+, in newborn macaques. DNA vectors coding for gag, pol and nef genes of SlVmac239 and for Hl-lllB env were used to prime followed by boosting with recombinant, homologous HlV-1 gpl6O. Following challenge with nonpathogenic, homologous SHIV-vpu+, partial protection (as defined by no or low, transient cytoviremia) was observed in 20% of the animals that received DNA priming/protein boost vaccination and in 3 of 4 animals given the gpl6O boosts only. These partially protected animals had high neutralizing antibody titers at time of challenge. Six completely or partially protected animals were rechallenged 4 months later with homologous virus. All showed evidence of either rapid viral clearance or low viral loads, suggesting that protective immunity was long-lived. The same 6 vaccinated animals were rechallenged a third time with heterologous, pathogenic SHlV89.6P. Four of these 5 animals maintained normal CD4+ T-cell counts and showed evidence of limited virus infection. Neutralizing antibody titers, T-cell proliferation and T-cytolytic T lymphocyte-responses offer evidence that both humoral and cellular immune mechanism contributed to the observed protection against pathogenic virus challenge. Our results indicate that DNA priming alone can induce antibody responses in newborn macaques and that protein boosts can induce some degree of protective immunity against viral challenge with both homologous and heterologous SHIV.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA376566
Entities
People
- Ruth M. Ruprecht
Organizations
- Dana–Farber Cancer Institute