Characterization of Humoral and Cellular Immune Responses Elicited by a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine in Healthy Adults (IPCAVD 001)

被引：95

作者：

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

Liu, Jinyan ^{[1
]}

Peter, Lauren ^{[1
]}

Abbink, Peter ^{[1
]}

Iampietro, M. Justin ^{[1
]}

Cheung, Ann ^{[1
]}

Alter, Galit ^{[2
]}

Chung, Amy ^{[2
]}

Dugast, Anne-Sophie ^{[2
]}

Frahm, Nicole ^{[4
]}

McElrath, M. Juliana ^{[4
]}

Wenschuh, Holger ^{[5
]}

Reimer, Ulf ^{[5
]}

Seaman, Michael S. ^{[1
,2
]}

Pau, Maria G. ^{[6
]}

Weijtens, Mo ^{[6
]}

Goudsmit, Jaap ^{[6
]}

Walsh, Stephen R. ^{[1
,2
,3
]}

Dolin, Raphael ^{[1
,2
,3
]}

Baden, Lindsey R. ^{[1
,2
,3
]}

机构：

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

[2] Ragon Inst MGH MIT & Harvard, Boston, MA USA

[3] Brigham & Womens Hosp, Boston, MA 02115 USA

[4] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA

[5] JPT Peptide Technol, Berlin, Germany

[6] Crucell Holland, Leiden, Netherlands

来源：

JOURNAL OF INFECTIOUS DISEASES | 2013年 / 207卷 / 02期

基金：

比尔及梅琳达.盖茨基金会; 美国国家卫生研究院;

关键词：

HIV-1; Vaccine; Adenovirus; 26; Immunogenicity; RHESUS-MONKEYS; T-CELLS; EFFICACY TRIAL; GENE-TRANSFER; DOUBLE-BLIND; VECTORS; INFECTION; STEP; CHALLENGES; ANTIBODIES;

D O I：

10.1093/infdis/jis671

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background. Adenovirus serotype 26 (Ad26) has been developed as a novel candidate vaccine vector for human immunodeficiency virus type 1 (HIV-1) and other pathogens. The primary safety and immunogenicity data from the Integrated Preclinical/Clinical AIDS Vaccine Development Program (IPCAVD) 001 trial, the first-in-human evaluation of a prototype Ad26 vector-based vaccine expressing clade A HIV-1 Env (Ad26.ENVA.01), are reported concurrently with this article. Here, we characterize in greater detail the humoral and cellular immune responses elicited by Ad26.ENVA.01 in humans. Methods. Samples from the IPCAVD 001 trial were used for humoral and cellular immunogenicity assays. Results. We observed a dose-dependent expansion of the magnitude, breadth, and epitopic diversity of Env-specific binding antibody responses elicited by this vaccine. Antibody-dependent cell-mediated phagocytosis, virus inhibition, and degranulation functional activity were also observed. Env-specific cellular immune responses induced by the vaccine included multiple CD8(+) and CD4(+) T-lymphocyte memory subpopulations and cytokine secretion phenotypes, although cellular immune breadth was limited. Baseline vector-specific T-lymphocyte responses were common but did not impair Env-specific immune responses in this study. Conclusion. Ad26.ENVA.01 elicited a broad diversity of humoral and cellular immune responses in humans. These data support the further clinical development of Ad26 as a candidate vaccine vector.

引用

页码：248 / 256

页数：9

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