Important note: Information in this article was accurate in 1994. The state of the art may have changed since the publication date.
SIV-GP120 recombinant viruses are avirulent and immunogenic.
Symp Nonhum Primate Models AIDS. 1993 Sep 19-22;11:abstract no. 60. Unique Identifier : AIDSLINE PRIM11/94191656 Lohman BL; Van Rompay KK; McChesney MB; McGowan E; Joye S; Luciw P; Marthas M; Pedersen NC; California Regional Primate Research Center, University of; California, Davis 95616.
Abstract:
The molecularly cloned SIVmac1A11 is a model for a live virus vaccine because rhesus macaques infected with this virus are transiently viremic, do not develop disease, and withstand low-dose challenge with a pathogenic strain of SIVmac. The molecular clone SIVmac239 causes persistent viremia and a fatal immunodeficiency disease in macaques. Recombinant viruses constructed with reciprocal exchanges of the surface envelope from the genomes of 1A11 and 239 produce low-level persistent viremia and no disease 2 years after infection. We have evaluated these viruses as vaccines. Effectiveness was based on SIV-specific cellular and humoral immune responses before and after IV challenge with uncloned SIVmac251. Two years after initial infection 2 of 4 macaques infected with 1A11 and all macaques infected with the recombinant viruses had detectable CTL responses against p55-gag and gp160-env. None of the monkeys had SIV neutralization titers greater than 1:100. Following IV challenge with SIVmac251, all monkeys immunized with SIVmac1A11 became infected; 3 with persistent, high level viremia (> 10 TCID50 per 10(6) PBMC) while one was transiently infected (virus isolation negative after 2 weeks post challenge (pc)). Two of 3 monkeys immunized with the recombinant containing 239 env in 1A11 background were infected; one with persistent high level viremia, one with transient viremia. One remains virus isolation negative. Two out of 3 monkeys immunized with the recombinant containing 1A11 env in 239 background were infected; both with low level viremia (< or = 10 TCID50 per 10(6) PBMC). One monkey remains virus isolation negative. Lymph node biopsies were taken at 12 weeks pc for quantitation of virus load as a measure of persistent infection and the cultures are in progress. It appears the low level persistent viremia with these envelope recombinants increases their immunogenicity compared to SIVmac1A11.
Keywords: Animal Genes, env Genes, gag HIV Envelope Protein gp120/*IMMUNOLOGY Lymph Nodes/MICROBIOLOGY/PATHOLOGY Macaca mulatta Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/PATHOLOGY/ PREVENTION & CONTROL SIV/GENETICS/*IMMUNOLOGY/PATHOGENICITY T-Lymphocytes, Cytotoxic/IMMUNOLOGY Vaccines, Synthetic/*THERAPEUTIC USE Viral Vaccines/*THERAPEUTIC USE Viremia/IMMUNOLOGY/PATHOLOGY Virulence ABSTRACT 940730
M9470862
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