Vladimir Temchura1, Klaus Überla. 1. Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Abstract
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response. RECENT FINDINGS: Comparing CD4 T-cell responses in HIV-infected individuals with and without neutralizing antibody breadth suggests that robust Gag-specific CD4 T cells may provide important T-cell help to Env-specific B cells. In a murine model, GagPol-specific T-helper cells were shown to provide intrastructural help for HIV-Env-specific antibody responses after immunization with a virus-like particle vaccine. GagPol-specific T-helper cells imprinted the IgG subtype ratio observed for Gag onto the HIV-Env antibody response and modulated the glycosylation pattern of the HIV Env-specific antibodies. SUMMARY: Intrastructural help is a promising strategy to improve overall levels and Fc-effector functions of the HIV-Env antibody response.
PURPOSE OF REVIEW: The importance of IgG Fc-effector functions for the efficacy of HIV vaccines is increasingly recognized. Although different types of vaccines were shown to induce antibodies with different Fc-activities, there is no clear strategy how to raise antibody responses with a desired pattern of Fc-effector functions. Given the central role of T-helper cells in regulating the germinal center reaction and the differentiation of B cells in an antigen-specific manner, the review will discuss whether T-helper cells directed against non-HIV envelope (Env) antigens could be harnessed to improve the HIV-Env antibody response. RECENT FINDINGS: Comparing CD4 T-cell responses in HIV-infected individuals with and without neutralizing antibody breadth suggests that robust Gag-specific CD4 T cells may provide important T-cell help to Env-specific B cells. In a murine model, GagPol-specific T-helper cells were shown to provide intrastructural help for HIV-Env-specific antibody responses after immunization with a virus-like particle vaccine. GagPol-specific T-helper cells imprinted the IgG subtype ratio observed for Gag onto the HIV-Env antibody response and modulated the glycosylation pattern of the HIV Env-specific antibodies. SUMMARY: Intrastructural help is a promising strategy to improve overall levels and Fc-effector functions of the HIV-Env antibody response.
Authors: Rajesh P Ringe; Victor M Cruz Portillo; Pia Dosenovic; Thomas J Ketas; Gabriel Ozorowski; Bartek Nogal; Lautaro Perez; Celia C LaBranche; Jillian Lim; Erik Francomano; Ian A Wilson; Rogier W Sanders; Andrew B Ward; David C Montefiori; Michel C Nussenzweig; P J Klasse; Albert Cupo; John P Moore Journal: J Virol Date: 2020-02-28 Impact factor: 5.103
Authors: Ehsan Suleiman; Julia Mayer; Elisabeth Lehner; Bianca Kohlhauser; Alexandra Katholnig; Mirjam Batzoni; Dominik Damm; Vladimir Temchura; Andreas Wagner; Klaus Überla; Karola Vorauer-Uhl Journal: Pharmaceutics Date: 2020-10-16 Impact factor: 6.525