4.5 Article

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

Journal

VACCINE
Volume 29, Issue 39, Pages 6763-6770

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2010.12.055

Keywords

SHIV; DNA vaccine; RANTES; Clade C

Funding

  1. National Institutes of Health (NIH) [N01-AI-50010, P01-A1-071739, R01-A1-071186]
  2. NIH/NIAID/DAIDS [HHSN272200800063C]

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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-gamma 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. (C) 2010 Elsevier Ltd. All rights reserved.

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