Most rhesus macaques infected with the CCR5-tropic SHIVAD8 generate cross-reactive antibodies that neutralize multiple HIV-1 strains

被引：62

作者：

Shingai, Masashi ^{[1
]}

Donau, Olivia K. ^{[1
]}

Schmidt, Stephen D. ^{[2
]}

Gautam, Rajeev ^{[1
]}

Plishka, Ronald J. ^{[1
]}

Buckler-White, Alicia ^{[1
]}

Sadjadpour, Reza ^{[1
]}

Lee, Wendy R. ^{[1
]}

LaBranche, Celia C. ^{[3
]}

Montefiori, David C. ^{[3
]}

Mascola, John R. ^{[2
]}

Nishimura, Yoshiaki ^{[1
]}

Martin, Malcolm A. ^{[1
]}

机构：

[1] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA

[2] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA

[3] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 48期

基金：

美国国家卫生研究院;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; RAPID DEVELOPMENT; TYPE-1; INFECTION; CELLS; MONKEYS; VACCINE; ISOLATE; BROAD; SERA; PATHOGENICITY;

D O I：

10.1073/pnas.1217443109

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The induction of broadly reacting neutralizing antibodies has been a major goal of HIV vaccine research. Characterization of a pathogenic CCR5 (R5)-tropic SIV/HIV chimeric virus (SHIV) molecular clone (SHIVAD8-EO) revealed that eight of eight infected animals developed cross-reactive neutralizing antibodies (NAbs) directed against an envelope glycoprotein derived from the heterologous HIV-1(DH12) strain. A panel of plasmas, collected from monkeys inoculated with either molecularly cloned or uncloned SHIVAD8 stocks, exhibited cross-neutralization against multiple tier 1 and tier 2 HIV-1 clade B isolates. One SHIVAD8-infected animal also developed NAbs against clades A and C HIV-1 strains. In this particular infected macaque, the cross-reacting anti-HIV-1 NAbs produced between weeks 7 and 13 were directed against a neutralization-sensitive virus strain, whereas neutralizing activities emerging at weeks 41-51 targeted more neutralization-resistant HIV-1 isolates. These results indicate that the SHIVAD8 macaque model represents a potentially valuable experimental system for investigating B-cell maturation and the induction of cross-reactive NAbs directed against multiple HIV-1 strains.

引用

页码：19769 / 19774

页数：6

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