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

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

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Animals
  • Cell Line, Tumor
  • Female
  • HEK293 Cells
  • HIV Antibodies / immunology*
  • HIV-1 / immunology*
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • T-Lymphocytes, Helper-Inducer / immunology*
  • env Gene Products, Human Immunodeficiency Virus / immunology*
  • gag Gene Products, Human Immunodeficiency Virus / immunology*
  • pol Gene Products, Human Immunodeficiency Virus / immunology*

Substances

  • AIDS Vaccines
  • HIV Antibodies
  • env Gene Products, Human Immunodeficiency Virus
  • gag Gene Products, Human Immunodeficiency Virus
  • pol Gene Products, Human Immunodeficiency Virus