GagPol-specific CD4+T-cells increase the antibody response to Env by intrastructural help

Ghulam Nabi,Matthias Tenbusch,Dan H Barouch,Klaus Überla,Vladimir Temchura,Oliver Gardt,Michael Storcksdieck Genannt Bonsmann

doi:10.1186/1742-4690-10-117

Abstract

BackgroundImmunization of rhesus macaques against Gag of SIV resulted in a more rapid appearance of Env antibodies after infection with SIV or SHIV challenge viruses although the vaccines lacked an Env component. We therefore explored whether T helper cells specific for internal HIV proteins could provide intrastructural help for Env-specific B cells and thus increase the Env antibody response.ResultsMice were immunized by adenoviral vector or DNA vaccines against GagPol and then boosted with virus-like particles (VLP) containing GagPol and Env. Env-specific antibody levels after the VLP booster immunizations were significantly higher in GagPol-immunized mice than in mock-vaccinated controls. Adoptive transfer of CD4+ T cells from GagPol-immunized mice also enhanced the Env antibody response to VLP immunization in the recipient mice. Depending on the presence of VLPs, co-cultivation of CD4+ T cells from GagPol-primed mice with BCR transgenic B cells specific for a protein presented on the surface of the VLPs also resulted in the activation of the B and T cells.ConclusionsOur study indicates that GagPol-specific T helper cells may provide intrastructural help for Env antibody responses. This cross-talk between immune responses directed against different components of the retroviral particle may be relevant for the immunopathogenesis of retroviral infections and allow to improve virus like particle vaccine approaches against HIV.

Highlights

Immunization of rhesus macaques against Gag of SIV resulted in a more rapid appearance of Env antibodies after infection with SIV or SHIV challenge viruses the vaccines lacked an Env component
Macaques had been immunized with different serotypes of adenoviral vectors encoding SIV Gag either as a homologous or heterologous prime boost regimen inducing a broad spectrum of Gag-specific T cell responses [2]
That GagPol specific CD4+ T cells provide help to B cells specific for surface protein of viral particles we further studied the interaction of B cells and T cells in vitro

Summary

Introduction

Immunization of rhesus macaques against Gag of SIV resulted in a more rapid appearance of Env antibodies after infection with SIV or SHIV challenge viruses the vaccines lacked an Env component. Given the higher-order structures viral proteins are enclosed in, these interactions may be relevant for immune control and immune escape Suggestive evidence for such a cross-talk of immune responses directed against different lentiviral proteins has been obtained in vaccine studies, in which non-human primates were immunized against Gag of SIV and subsequently challenged with SIV or SIV-HIV. Gag-specific T helper cells induced by vaccination could provide cognate help for Env-specific B cells and accelerate the production of Env-specific antibody responses early after infection To test this hypothesis, we re-analysed data from a nonhuman primate study, performed immunization and T cell transfer experiments in mice, and explored intrastructural help by in vitro B and T cell co-culture experiments

Methods

Results

Discussion

Conclusion