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PMID: 15731230 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Protection of rhesus monkeys against infection with minimally pathogenic simian-human immunodeficiency virus: correlations with neutralizing antibodies and cytotoxic T cells.

Journal of virology ·Vol. 79 ·No. 6 ·2005-03-00 ·Pages 3358-69

Quinnan GV, Yu XF, Lewis MG, Zhang PF, Sutter G, Silvera P, Dong M, Choudhary A, Sarkis PT, Bouma P, Zhang Z, Montefiori DC, Vancott TC, Broder CC

Abstract

We studied the capacity of active immunization of rhesus monkeys with HIV-1 envelope protein (Env) to induce primary virus cross-reactive neutralizing antibodies to prevent infection following intravenous challenge with simian-human immunodeficiency virus (SHIV). Monkeys were immunized with the human immunodeficiency type 1 (HIV-1) strain R2 Env. Initially, the Env was expressed in vivo by an alphavirus replicon particle system, and then it was administered as soluble oligomeric gp140. Concurrently, groups of monkeys received expression vectors that encoded either simian immunodeficiency virus (SIV) gag/pol genes or no SIV genes in vivo to test the additional protective benefit of concurrent induction of virus-specific cell-mediated immune (CMI) responses. Groups of control monkeys received either the gag/pol regimen or sham immunizations. The antibodies induced by the Env immunization regimen neutralized diverse primary HIV-1 strains. Similarly, potent CMI responses were induced by the gag/pol regimen, as measured by gamma interferon enzyme-linked immunospot assays. Differences in the responses among groups of monkeys strongly suggested that there was interference between the Env and gag/pol immunization regimens. Complete protection of some of the monkeys against infection after intravenous challenge with the partially pathogenic SHIV(DH12R (Clone 7)) was associated independently with both neutralizing antibody and CMI responses. Protection was associated with SHIV(DH12 (Clone 7)) serum neutralizing antibody titers of > or =1:80 or with cellular immune responses corresponding to >2,000 spot forming cells per 10(6) peripheral blood mononuclear cells. Immunization was also associated with a reduction in the magnitude and duration of virus load. Induction of cross-reactive, primary HIV-1-neutralizing antibodies is feasible and, when potent, may result in complete protection against infection with a heterologous challenge virus strain.

MeSH Terms
AIDS Vaccines/immunology Animals Antibodies, Viral/blood Disease Models, Animal Gene Products, env/immunology Gene Products, gag HIV Antibodies/blood HIV Infections/prevention & control HIV-1/genetics,immunology Macaca mulatta Neutralization Tests Simian Acquired Immunodeficiency Syndrome/prevention & control Simian Immunodeficiency Virus/genetics,immunology T-Lymphocytes, Cytotoxic/immunology Viral Load
Chemicals
AIDS Vaccines Antibodies, Viral Gene Products, env Gene Products, gag HIV Antibodies
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Quinnan Gerald V
Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd., Bethesda, MD 20814, USA. gquinnan@usuhs.mil
Yu Xiao-Fang
Lewis Mark G
Zhang Peng Fei
Sutter Gerd
Silvera Peter
Dong Ming
Choudhary Anil
Sarkis Phuong T N
Bouma Peter
Zhang Zhiqiang
Montefiori David C
Vancott Thomas C
Broder Christopher C
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.79.6.3358-3369.2005
Email
gquinnan@usuhs.mil
Published
2005-03-00
Pages
3358-69
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1075715
Subset
IM
Grants
NIAID NIH HHS · P01 AI048280 · United States
NIAID NIH HHS · R01 AI037438 · United States
NIAID NIH HHS · 1 R01 AI37438 · United States
NIAID NIH HHS · 1 PO1 AI48280 · United States
External Links
PubMed source DOI: 10.1128/JVI.79.6.3358-3369.2005 PMC Full Text View journal details
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