Evaluation of immune responses induced by HIV-1 gp120 in rhesus macaques: effect of vaccination on challenge with pathogenic strains of homologous and heterologous simian human immunodeficiency viruses.
The simian human immunodeficiency virus (SHIV) macaque model of AIDS has provided a very useful system for evaluation of envelope-based candidate vaccines against HIV-1. Eight rhesus macaques were immunized with monomeric recombinant gp120 of HIV-1(LAI) (rgp120) and used to evaluate whether this vaccine conferred protection against challenge with pathogenic SHIVs (SHIV(KU-2) and SHIV(89.6)P). The vaccinated macaques developed high titers of antibodies against rgp120 that reacted efficiently with the envelope proteins of homologous SHIV (SHIV(KU-2)) and poorly with the SHIV(89.6)P envelope, a heterologous strain of SHIV. This vaccine also induced neutralizing antibodies but only against SHIV(KU-2). Vaccine-induced antibodies were of high avidity and predominantly against linear epitopes on the protein. Vaccinated macaques developed gp120-specific T-helper cells but no consistent cytotoxic T lymphocytes. However, cellular immune responses were short-lived in all eight vaccinates. At week 22 postimmunization, four vaccinates were challenged with SHIV(KU-2) and the other four with SHIV(89.6)P. Four unvaccinated control macaques were also infected: two with SHIV(KU-2) and two with SHIV(89.6)P. Vaccinated macaques generally showed anamnestic antibody and T-helper cell responses. However, T-helper responses were again short-lived. Upon challenge, the level of productive virus replication was indistinguishable between vaccine and control groups, suggesting that rgp120 did not confer protection against virus replication when animals were challenged with homologous or heterologous SHIV viruses.
Laboratory of Viral Pathogenesis, Department of Microbiology, MolecularGenetics, and Immunolgy, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. Akumar@kumc.edu
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Kumar
J D
JD
Lifson
P S
PS
Silverstein
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Jia
D
D
Sheffer
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Z
Li
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Narayan
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D000915:Antibody Affinity; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008253:Macaca mulatta; D009500:Neutralization Tests; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology
D016915:AIDS Vaccines; D018985:Epitopes, B-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D014614:Vaccines, Synthetic