High antibody and cellular responses induced to HIV-1 clade C envelope following DNA vaccines delivered by electroporation

Vaccine. 2011 Sep 9;29(39):6763-70. doi: 10.1016/j.vaccine.2010.12.055. Epub 2010 Dec 31.

Abstract

Background: Clade C is the predominant HIV-1 strain infecting people in sub-Saharan Africa, India, and China and there is a critical need for a vaccine targeted to these areas. In this study we tested a DNA based vaccine that encodes the SIVgag, SIVpol and HIV-1 envelope clade C.

Methods: Rhesus macaques were immunized by electroporation with the DNA plasmid encoding optimized SIVgag, SIVpol and an HIV-1 env clade C with or without the adjuvant RANTES. Animals were monitored for immune responses and challenged following the final immunization with 25 animal infectious doses (AID) of SHIV-1157ipd3N4.

Results: We found that the vaccine induced high levels of antigen specific IFN-γ producing effector cells and the capacity for CD4+ and CD8+ to proliferate upon antigen stimulation. Importantly, we found that the vaccine induced antibody titers as high as 1/4000. These antibodies were capable of neutralizing tier 1 HIV-1 viruses. Finally, when macaques were challenged with SHIV, viral loads were controlled in vaccinated groups.

Conclusion: We conclude that immunization with a simian/human immunodeficiency virus DNA-based vaccine delivered by electroporation can induce cellular and humoral immune responses that are able to control viral replication.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / immunology*
  • Adjuvants, Immunologic
  • Animals
  • Antibody Formation*
  • Chemokine CCL5 / immunology
  • Electroporation / methods
  • Enzyme-Linked Immunospot Assay
  • Genes, env
  • Genes, gag
  • Genes, pol
  • HIV Antibodies / immunology
  • HIV Infections / immunology
  • HIV Infections / prevention & control*
  • HIV-1 / genetics
  • HIV-1 / immunology*
  • HIV-1 / pathogenicity
  • Humans
  • Immunity, Cellular*
  • Immunity, Humoral
  • Immunologic Memory
  • Interferon-gamma / immunology
  • Macaca mulatta
  • Neutralization Tests
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / immunology
  • T-Lymphocytes / immunology
  • Vaccination
  • Vaccines, DNA / administration & dosage
  • Vaccines, DNA / immunology*
  • Viral Load

Substances

  • AIDS Vaccines
  • Adjuvants, Immunologic
  • Chemokine CCL5
  • HIV Antibodies
  • Vaccines, DNA
  • Interferon-gamma