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

被引：52

作者：

Bogers, Willy M. J. M. ^{[1
]}

Davis, David ^{[1
]}

Baak, Ilona ^{[1
]}

Kan, Elaine ^{[2
]}

Hofman, Sam ^{[1
]}

Sun, Yide ^{[2
]}

Mortier, Daniella ^{[1
]}

Lian, Ying ^{[2
]}

Oostermeijer, Herman ^{[1
]}

Fagrouch, Zahra ^{[1
]}

Dubbes, Rob ^{[1
]}

van der Maas, Martin ^{[1
]}

Mooij, Petra ^{[1
]}

Koopman, Gerrit ^{[1
]}

Verschoor, Ernst ^{[1
]}

Langedijk, Johannes P. M. ^{[3
]}

Zhao, Jun ^{[4
]}

Brocca-Cofano, Egidio ^{[4
]}

Robert-Guroff, Marjorie ^{[4
]}

Srivastava, Indresh ^{[2
]}

Barnett, Susan ^{[2
]}

Heeney, Jonathan L. ^{[1
,5
]}

机构：

[1] BPRC, Dept Virol, NL-2280 GH Rijswijk, Netherlands

[2] Novartis, Emeryville, CA 94608 USA

[3] Pepscan therapeut BV, Lelystad, Netherlands

[4] NCI, Vaccine Branch, Bethesda, MD 20892 USA

[5] Univ Cambridge, Cambridge CB3 0ES, England

来源：

VIROLOGY | 2008年 / 382卷 / 02期

基金：

美国国家卫生研究院;

关键词：

HIV vaccine; Animal model; Mucosal challenge; Nabs; ADCC;

D O I：

10.1016/j.virol.2008.09.016

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

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-1(89.6p) env gene. Following boosting with either heterologous recombinant protein or alphavirus replicons at 12-week intervals animals were intrarectally exposed to infections doses of the CCR5 tropic SHIV(SF162p4). 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-F-cell responses, but rather with the Nab titer prior to exposure. (C) 2008 Elsevier Inc. All rights reserved.

引用

页码：217 / 225

页数：9

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