Protective Efficacy of a Global HIV-1 Mosaic Vaccine against Heterologous SHIV Challenges in Rhesus Monkeys

被引：295

作者：

Barouch, Dan H. ^{[1
,2
]}

Stephenson, Kathryn E. ^{[1
]}

Borducchi, Erica N. ^{[1
]}

Smith, Kaitlin ^{[1
]}

Stanley, Kelly ^{[1
]}

McNally, Anna G. ^{[1
]}

Liu, Jinyan ^{[1
]}

Abbink, Peter ^{[1
]}

Maxfield, Lori F. ^{[1
]}

Seaman, Michael S. ^{[1
]}

Dugast, Anne-Sophie ^{[2
]}

Alter, Galit ^{[2
]}

Ferguson, Melissa ^{[3
]}

Li, Wenjun ^{[4
]}

Earl, Patricia L. ^{[5
]}

Moss, Bernard ^{[5
]}

Giorgi, Elena E. ^{[6
]}

Szinger, James J. ^{[6
]}

Eller, Leigh Anne ^{[7
]}

Billings, Erik A. ^{[7
]}

Rao, Mangala ^{[7
]}

Tovanabutra, Sodsai ^{[7
]}

Sanders-Buell, Eric ^{[7
]}

Weijtens, Mo ^{[8
]}

Pau, Maria G. ^{[8
]}

Schuitemaker, Hanneke ^{[8
]}

Robb, Merlin L. ^{[7
]}

Kim, Jerome H. ^{[7
]}

Korber, Bette T. ^{[6
]}

Michael, Nelson L. ^{[7
]}

机构：

[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[2] Ragon Inst MGH Massachusetts Inst Technol & Harva, Boston, MA 02114 USA

[3] Alpha Genesis Inc, Yemassee, SC 29945 USA

[4] Univ Massachusetts, Sch Med, Worcester, MA 01605 USA

[5] NIAID, Bethesda, MD 20892 USA

[6] Los Alamos Natl Lab, Los Alamos, NM 87545 USA

[7] Walter Reed Army Inst Res, US Mil HIV Res Program, Rockville, MD 20850 USA

[8] Crucell Holland BV, NL-2301 CA Leiden, Netherlands

来源：

CELL | 2013年 / 155卷 / 03期

基金：

美国国家卫生研究院;

关键词：

SIMIAN IMMUNODEFICIENCY VIRUS; T-LYMPHOCYTE RESPONSES; IMMUNE CONTROL; BREADTH; AIDS; IMMUNOGENICITY; DIVERSITY; INFECTION; MACAQUES; COVERAGE;

D O I：

10.1016/j.cell.2013.09.061

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine.

引用

页码：531 / 539

页数：9

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