Journal
JOURNAL OF IMMUNOLOGY
Volume 195, Issue 10, Pages 4861-4872Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1501377
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Funding
- Transregional Collaborative Research Grant from the Deutsche Forschungsgemeinschaft [TRR-60, TRR-130]
- Collaboration for AIDS Vaccine Discovery Grant through the Bill & Melinda Gates Foundation [OPP1040727, OPP1032817]
- Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. [W81XWH-11-2-0174]
- U. S. Department of Defense
- Ruhr-University Research School
- science exchange grant within the Collaboration for AIDS Vaccine Discovery of the Bill & Melinda Gates Foundation
- Bill and Melinda Gates Foundation [OPP1040727] Funding Source: Bill and Melinda Gates Foundation
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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 Fc gamma R 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.
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