The improved antibody response against HIV-1 after a vaccination based on intrastructural help is complemented by functional CD8+ T cell responses

Autor: Drew Hannaman, Klaus Überla, Michael Storcksdieck genannt Bonsmann, Matthias Tenbusch, Thomas Niezold
Rok vydání: 2015
Předmět:
0301 basic medicine
viruses
T cell
Immunization
Secondary
HIV Infections
Vaccinia virus
CD8-Positive T-Lymphocytes
HIV Antibodies
gag Gene Products
Human Immunodeficiency Virus
Immunoglobulin G
DNA vaccination
03 medical and health sciences
Mice
0302 clinical medicine
Immune system
medicine
Vaccines
DNA
Cytotoxic T cell
Animals
030212 general & internal medicine
Vaccines
Virus-Like Particle
AIDS Vaccines
Immunity
Cellular
Mice
Inbred BALB C
General Veterinary
General Immunology and Microbiology
biology
Vaccination
Public Health
Environmental and Occupational Health
env Gene Products
Human Immunodeficiency Virus
virus diseases
Virology
Immunity
Humoral
030104 developmental biology
Infectious Diseases
medicine.anatomical_structure
Electroporation
pol Gene Products
Human Immunodeficiency Virus
Immunology
Antibody Formation
biology.protein
HIV-1
Molecular Medicine
Cytokines
Antibody
CD8
Zdroj: Vaccine. 34(15)
ISSN: 1873-2518
Popis: 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.
Databáze: OpenAIRE
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