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

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.