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J Immunol. 2015 Nov 15;195(10):4861-72. doi: 10.4049/jimmunol.1501377. Epub 2015 Oct 14.

Enhancing the Quality of Antibodies to HIV-1 Envelope by GagPol-Specific Th Cells.

Author information

1
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum 44801, Germany;
2
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum 44801, Germany; Universitätsklinikum Erlangen, Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany;
3
U.S. Military HIV Research Program, Silver Spring, MD 20910;
4
Department of Medical Microbiology and Hygiene, Institute of Virology, University Medical Center Freiburg, Freiburg 79106, Germany;
5
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755; and.
6
Ichor Medical Systems, Inc., San Diego, CA 92121.
7
Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum 44801, Germany; Universitätsklinikum Erlangen, Institut für Klinische und Molekulare Virologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen 91054, Germany; klaus.ueberla@fau.de.

Abstract

The importance of Fc-dependent effector functions of Abs induced by vaccination is increasingly recognized. However, vaccination of mice against HIV envelope (Env) induced a skewed Th cell response leading to Env-specific Abs with reduced effector function. To overcome this bias, GagPol-specific Th cells were harnessed to provide intrastructural help for Env-specific B cells after immunization with virus-like particles containing GagPol and Env. This led to a balanced Env-specific humoral immune response with a more inflammatory Fc glycan profile. The increased quality in the Ab response against Env was confirmed by FcγR activation assays. Because the Env-specific Th cell response was also biased in human vaccinees, intrastructural help is an attractive novel approach to increase the efficacy of prophylactic HIV Env-based vaccines and may also be applicable to other particulate vaccines.

PMID:
26466954
DOI:
10.4049/jimmunol.1501377
[Indexed for MEDLINE]
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