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Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1

Eva K. L. Nordström^1,2,

Mattias N. E. Forsell^1,2,

¹ Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden
² Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden
³ MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford, UK

Correspondence
Gunilla B. Karlsson
Nilla.Karlsson{at}mtc.ki.se

With the human immunodeficiency virus type 1 (HIV-1) epidemic expanding at increasing speed, development of a safe and effective vaccine remains a high priority. One of the most central vaccine platforms considered is plasmid DNA. However, high doses of DNA and several immunizations are typically needed to achieve detectable T-cell responses. In this study, a Semliki Forest virus replicon DNA vaccine designed for human clinical trials, DREP.HIVA, encoding an antigen that is currently being used in human trials in the context of a conventional DNA plasmid, pTHr.HIVA, was generated. It was shown that a single immunization of DREP.HIVA stimulated HIV-1-specific T-cell responses in mice, suggesting that the poor immunogenicity of conventional DNA vaccines may be enhanced by using viral replicon-based plasmid systems. The results presented here support the evaluation of Semliki Forest virus replicon DNA vaccines in non-human primates and in clinical studies.

These authors contributed equally.

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