A synergistic effect of a combined bivalent DNA-protein anti-HIV-1 vaccine containing multiple T- and B-cell epitopes of HIV-1 proteins

Mol Immunol. 2008 Feb;45(3):661-9. doi: 10.1016/j.molimm.2007.07.016. Epub 2007 Sep 14.

Abstract

Immunogenic properties of the combined vaccine CombiHIVvac, comprising polyepitope HIV-1 immunogens, one being the artificial polyepitope protein TBI, containing the T- and B-cell epitopes from Env and Gag proteins, and the DNA vaccine construct pcDNA-TCI coding for the artificial protein TCI, carrying over 80 T-cell epitopes (both CD4+ CTL and CD8+ Th) from Env, Gag, Pol, and Nef proteins, are studied in this work. The data reported demonstrate clearly that a combination of two B- and T-cell immunogens (TBI and TCI) in one construct results in a synergistic increase in the antibody response to both TBI protein and the proteins from HIV-1 lysate. The level of antibodies induced by immunization with the constructs containing either immunogen alone (TBI protein or the plasmid pcDNA-TCI) was significantly lower as compared to that induced by the combined vaccine. The analysis performed suggests that the presence of CD4+ T-helper epitopes, which can be presented by MHC class II, in the protein TCI may be the main reason underlying the increased synthesis of antibodies to TBI protein due to a CD4-mediated stimulation of B-cell proliferation and differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / agonists*
  • AIDS Vaccines / genetics
  • AIDS Vaccines / immunology
  • Animals
  • Antibodies, Viral / immunology*
  • Antibody Formation / immunology*
  • Antigen Presentation / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Epitopes, B-Lymphocyte / genetics
  • Epitopes, B-Lymphocyte / immunology*
  • Epitopes, T-Lymphocyte / genetics
  • Epitopes, T-Lymphocyte / immunology*
  • HIV-1 / immunology*
  • Histocompatibility Antigens Class II / immunology
  • Mice
  • Mice, Inbred BALB C
  • Vaccines, DNA / genetics
  • Vaccines, DNA / immunology
  • Viral Proteins / genetics
  • Viral Proteins / immunology*

Substances

  • AIDS Vaccines
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Vaccines, DNA
  • Viral Proteins