11145906

pubmed:Citation

1

Four rhesus macaques were sequentially immunized with live vaccines DeltavpuDeltanefSHIV-4 (vaccine-I) and Deltavpu SHIV(PPC) (vaccine-II). The vaccine viruses did not replicate productively in the peripheral blood mononuclear cells (PBMCs) of the vaccinated animals. All four animals developed binding antibodies against both the vaccine-I and -II envelope glycoproteins but neutralizing antibodies only against vaccine-I. They developed vaccine virus-specific CTLs that also recognized homologous as well as heterologous pathogenic SHIVs. Thirty weeks after the last immunization, the vaccinated animals and three unvaccinated control animals were challenged iv with a highly virulent heterologous SHIV(89.6)P. As expected, the three unvaccinated control animals developed large numbers of infectious PBMCs, high plasma viremia, and precipitous loss of CD4(+) T cells. Two controls did not develop any immune response and succumbed to AIDS in about 6 months. The third control animal developed neutralizing antibodies and had a more chronic disease course, but eventually succumbed to AIDS-related complications 81 weeks after inoculation. The four vaccinated animals became infected with challenge virus as indicated by the presence of challenge virus-specific DNA in the PBMCs and RNA in plasma. However, virus in these animals replicated approximately 200- to 60,000-fold less efficiently than in control animals and eventually, plasma viral RNA became undetectable in three of the four vaccinates. The animals maintained normal CD4(+) T-cell levels throughout the observation period of 85 weeks after a transient drop at Week 3 postchallenge. They also maintained CTL responses throughout the observation period. These studies thus showed that the graded immunization schedule resulted in a safe and highly effective long-lasting immune response that was associated with protection against AIDS by highly pathogenic heterologous SHIV(89.6)P.

eng

IM

MEDLINE

0042-6822

Copyright 2001 Academic Press.

5

NLM

241-56

pubmed-meshheading:11145906-AIDS Vaccines, pubmed-meshheading:11145906-Acquired Immunodeficiency Syndrome, pubmed-meshheading:11145906-Animals, pubmed-meshheading:11145906-Antibodies, Viral, pubmed-meshheading:11145906-CD4-Positive T-Lymphocytes, pubmed-meshheading:11145906-Cytotoxicity, Immunologic, pubmed-meshheading:11145906-DNA, Viral, pubmed-meshheading:11145906-Disease Models, Animal, pubmed-meshheading:11145906-HIV, pubmed-meshheading:11145906-HIV Antibodies, pubmed-meshheading:11145906-Immunization, pubmed-meshheading:11145906-Immunization Schedule, pubmed-meshheading:11145906-Lymph Nodes, pubmed-meshheading:11145906-Macaca mulatta, pubmed-meshheading:11145906-Neutralization Tests, pubmed-meshheading:11145906-RNA, Viral, pubmed-meshheading:11145906-Simian Acquired Immunodeficiency Syndrome, pubmed-meshheading:11145906-Simian immunodeficiency virus, pubmed-meshheading:11145906-T-Lymphocytes, Cytotoxic, pubmed-meshheading:11145906-Vaccines, Attenuated, pubmed-meshheading:11145906-Viral Load

Sequential immunization of macaques with two differentially attenuated vaccines induced long-term virus-specific immune responses and conferred protection against AIDS caused by heterologous simian human immunodeficiency Virus (SHIV(89.6)P).

Journal Article, Research Support, U.S. Gov't, P.H.S.