High antibody and cellular responses induced to HIV-1 clade C envelope following DNA vaccines delivered by electroporation |
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Authors: | Yin Jiangmei Dai Anlan Lecureux Jonathan Arango Tatiana Kutzler Michele A Yan Jian Lewis Mark G Khan Amir Sardesai Niranjan Y Montefiore David Ruprecht Ruth Weiner David B Boyer Jean D |
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Affiliation: | a Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd, 505 SCL, Philadelphia, PA 19104, United States b Drexel University, College of Medicine, 245N 15th Street, Philadelphia, PA 19102, United States c Research Section, Bioqual, Rockville, MD 20850, United States d Inovio Pharmaceuticals, 1787 Sentry Parkway West, Blue Bell, PA 19422, United States e Duke University, Durham, NC 27710, United States f Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, United States |
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Abstract: | BackgroundClade 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.MethodsRhesus 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.ResultsWe 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.ConclusionWe 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. |
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Keywords: | SHIV DNA vaccine RANTES Clade C |
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