Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys

被引：317

作者：

Barouch, Dan H. ^{[1
,2
,3
]}

O'Brien, Kara L. ^{[1
]}

Simmons, Nathaniel L. ^{[1
]}

King, Sharon L. ^{[1
]}

Abbink, Peter ^{[1
]}

Maxfield, Lori F. ^{[1
]}

Sun, Ying-Hua ^{[1
]}

La Porte, Annalena ^{[1
]}

Riggs, Ambryice M. ^{[1
]}

Lynch, Diana M. ^{[1
]}

Clark, Sarah L. ^{[1
]}

Backus, Katherine ^{[1
]}

Perry, James R. ^{[1
]}

Seaman, Michael S. ^{[1
]}

Carville, Angela ^{[4
]}

Mansfield, Keith G. ^{[4
]}

Szinger, James J. ^{[5
]}

Fischer, Will ^{[5
]}

Muldoon, Mark ^{[6
,7
]}

Korber, Bette ^{[5
,7
]}

机构：

[1] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MA 02215 USA

[2] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA

[3] Harvard Univ, Boston, MA 02115 USA

[4] New England Reg Primate Res Ctr, Southborough, MA 01772 USA

[5] Los Alamos Natl Lab, Los Alamos, NM USA

[6] Univ Manchester, Sch Math, Manchester, Lancs, England

[7] Santa Fe Inst, Santa Fe, NM 87501 USA

来源：

NATURE MEDICINE | 2010年 / 16卷 / 03期

基金：

美国国家卫生研究院;

关键词：

HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNOGENICITY; REPLICATION; VARIANTS; VECTORS; STEP;

D O I：

10.1038/nm.2089

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 worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development(1,2). Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity(3). Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1.

引用

页码：319 / U116

页数：6

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