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

GagPol 特异性 Th 细胞增强 HIV-1 包膜抗体的质量

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作者:Michael Storcksdieck genannt Bonsmann, Thomas Niezold, Vladimir Temchura, Franco Pissani, Katrin Ehrhardt, Eric P Brown, Nana Yaw Osei-Owusu, Drew Hannaman, Hartmut Hengel, Margaret E Ackerman, Hendrik Streeck, Ghulam Nabi, Matthias Tenbusch, Klaus Überla

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.

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