title: GagPol-specific CD4⁺ T-cells increase the antibody response to Env by intrastructural help.
abstract: BACKGROUND
  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 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.
  
  
  RESULTS
  Mice 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.
  
  
  CONCLUSIONS
  Our 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.
authors.forename: Ghulam
authors.initials: G
authors.lastname: Nabi
authors.forename: Michael Storcksdieck
authors.initials: MS
authors.lastname: Genannt Bonsmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Tenbusch
authors.forename: Oliver
authors.initials: O
authors.lastname: Gardt
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Vladimir
authors.initials: V
authors.lastname: Temchura
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Bochum, Germany. klaus.ueberla@rub.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Uberla
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D015686:Gene Products, env / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015684:Gene Products, pol / Q000276:immunology*; D007114:Immunization / Q000379:methods; D051379:Mice; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology
chemical_list: D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D058425:Vaccines, Virus-Like Particle