title: The improved antibody response against HIV-1 after a vaccination based on intrastructural help is complemented by functional CD8+ T cell responses.
abstract: Despite more than three decades of intense research, a prophylactic HIV-1 vaccine remains elusive. Four vaccine modalities have been evaluated in clinical efficacy studies, but only one demonstrated at least modest efficacy, which correlated with polyfunctional antibody responses to the HIV surface protein Env. To be most effective, a HIV-1 vaccine probably has to induce both, functional antibody and CD8(+) T cell responses. We therefore analyzed DNA/DNA and DNA/virus-like particle (VLP) regimens for their ability to induce humoral and cellular immune responses. Here, DNA vaccination of mice induced strong CD8(+) responses against Env and Gag. However, the humoral response to Env was dominated by IgG1, a subclass known for its low functionality. In contrast, priming only with the Gag-encoding plasmid followed by a boost with VLPs consisting of Gag and Env improved the quality of the anti-Env antibody response via intrastructural help (ISH) provided by Gag-specific T cells to Env-specific B cells. Furthermore, the Gag-specific CD8(+) T cells induced by the DNA prime immunization could still protect from a lethal infection with recombinant vaccinia virus encoding HIV Gag. Therefore, this immunization regimen represents a promising approach to combine functional antibody responses toward HIV Env with strong CD8(+) responses controlling early viral replication.
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Storcksdieck genannt Bonsmann
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Niezold
authors.affiliation: Ichor Medical Systems, Inc., San Diego, CA, USA.
authors.forename: Drew
authors.initials: D
authors.lastname: Hannaman
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany; Universitätsklinikum Erlangen, Institute of Clinical and Molecular Virology, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Überla
authors.affiliation: Department of Molecular and Medical Virology, Ruhr-University Bochum, Germany. Electronic address: Matthias.tenbusch@rub.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Tenbusch
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D000917:Antibody Formation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000276:immunology; D018274:Electroporation; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination / Q000379:methods*; D019444:Vaccines, DNA / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology; D014616:Vaccinia virus; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; D016207:Cytokines; D015483:HIV Antibodies; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D058425:Vaccines, Virus-Like Particle; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus
keywords: AIDS; Antibodies; CTLs; DNA; HIV-1; VLPs; Vaccine