Systemic neutralizing antibodies induced by long interval mucosally primed systemically boosted immunization correlate with protection from mucosal SHIV challenge

Abstract Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of...

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Published in:Virology (New York, N.Y.) N.Y.), 2008-12, Vol.382 (2), p.217-225
Main Authors: Bogers, Willy M.J.M, Davis, David, Baak, Ilona, Kan, Elaine, Hofman, Sam, Sun, Yide, Mortier, Daniella, Lian, Ying, Oostermeijer, Herman, Fagrouch, Zahra, Dubbes, Rob, van der Maas, Martin, Mooij, Petra, Koopman, Gerrit, Verschoor, Ernst, Langedijk, Johannes P.M, Zhao, Jun, Brocca-Cofano, Egidio, Robert-Guroff, Marjorie, Srivastava, Indresh, Barnett, Susan, Heeney, Jonathan L
Format: Article
Language:English
Subjects:
ADCC
Adenovirus
AIDS Vaccines - administration & dosage
Alphavirus
Animal model
Animals
Antibodies, Viral - biosynthesis
Base Sequence
DNA, Viral - analysis
DNA, Viral - genetics
Female
Genes, env
HIV Antibodies - biosynthesis
HIV Infections - immunology
HIV Infections - prevention & control
HIV Infections - virology
HIV vaccine
HIV-1 - genetics
HIV-1 - immunology
Human immunodeficiency virus 1
Immunity, Cellular
Immunity, Mucosal
Immunization Schedule
Immunization, Secondary
Infectious Disease
Macaca mulatta
Male
Mucosal challenge
Nabs
Neutralization Tests
SAIDS Vaccines - administration & dosage
Simian Acquired Immunodeficiency Syndrome - immunology
Simian Acquired Immunodeficiency Syndrome - prevention & control
Simian Acquired Immunodeficiency Syndrome - virology
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - immunology
Viremia - immunology
Viremia - prevention & control
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Summary:Abstract Immune correlates of vaccine protection from HIV-1 infection would provide important milestones to guide HIV-1 vaccine development. In a proof of concept study using mucosal priming and systemic boosting, the titer of neutralizing antibodies in sera was found to correlate with protection of mucosally exposed rhesus macaques from SHIV infection. Mucosal priming consisted of two sequential immunizations at 12-week intervals with replicating host range mutants of adenovirus type 5 (Ad5hr) expressing the HIV-189.6p env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infectious doses of the CCR5 tropic SHIVSF162p4 . Heterologous mucosal prime systemic boost immunization elicited neutralizing antibodies (Nabs), antibody-dependent cytotoxicity (ADCC), and specific patterns of antibody binding to envelope peptides. Vaccine induced protection did not correlate with the type of boost nor T-cell responses, but rather with the Nab titer prior to exposure.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2008.09.016