Enhanced immunogenicity using an alphavirus replicon DNA vaccine against human immunodeficiency virus type 1.
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.
Nordström
Eva K L
EKL
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.|Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Forsell
Mattias N E
MNE
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.|Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Barnfield
Christina
C
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.|Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Bonin
Eivor
E
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.
Hanke
Tomas
T
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, The John Radcliffe, Oxford, UK.
Sundström
Magnus
M
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.|Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Karlsson
Gunilla B
GB
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.|Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
Liljeström
Peter
P
Department of Vaccine Research, Swedish Institute for Infectious Disease Control, S-171 82 Solna, Sweden.|Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden.
D000818:Animals; D004279:DNA, Viral / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012093:Replicon / Q000276:immunology; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D004279:DNA, Viral; D019444:Vaccines, DNA; D014765:Viral Vaccines