Hepatitis C virus non-structural protein 3-specific cellular immune responses following single or combined immunization with DNA or recombinant Semliki Forest virus particles.
The capacity of recombinant Semliki Forest virus particles (rSFV) expressing the hepatitis C virus non-structural protein 3 (NS3) to induce, in comparison or in combination with an NS3-expressing plasmid, specific cellular and humoral immune responses in murine models was evaluated. In vitro studies indicated that both types of vaccine expressed the expected size protein, albeit with different efficacies. The use of mice transgenic for the human HLA-A2.1 molecule indicated that the rSFV-expressed NS3 protein induces, as shown previously for an NS3 DNA vaccine, NS3-specific cytotoxic lymphocytes (CTLs) targeted at one dominant HLA-A2 epitope described in infected patients. All DNA/rSFV vaccine combinations evaluated induced specific CTLs, which were detectable for up to 31 weeks after the first injection. Overall, less than 1 log difference was observed in terms of the vigour of the bulk CTL response induced and the CTL precursor frequency between all vaccines (ranging from 1:2.6x10(5) to 1:1x10(6)). Anti-NS3 antibodies could only be detected following a combined vaccine regimen in non-transgenic BALB/c mice. In conclusion, rSFV particles expressing NS3 are capable of inducing NS3-specific cellular immune responses targeted at a major HLA-A2 epitope. Such responses were comparable to those obtained with a DNA-based NS3 vaccine, whether in the context of single or combined regimens.
Brinster
C
C
Unité Mixte CNRS/BioMérieux UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France1.
Chen
M
M
Microbiology and Tumorbiology Center, Karolinska Institute, S-171 77 Stockholm, Sweden2.
Boucreux
D
D
Unité Mixte CNRS/BioMérieux UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France1.
Paranhos-Baccala
G
G
Centre Européen de Recherche en Virologie et en Immunologie, CNRS/BioMérieux UMR 2142, 21 avenue Tony Garnier, 69007 Lyon, France3.
Liljeström
P
P
Microbiology and Tumorbiology Center, Karolinska Institute, S-171 77 Stockholm, Sweden2.
Lemmonier
F
F
Institut Pasteur, Unité d'Immunité Cellulaire Antivirale, Département SIDA-Rétrovirus, 28 rue du Dr Roux, Paris, France4.
Inchauspé
G
G
Unité Mixte CNRS/BioMérieux UMR 2142, Ecole Normale Supérieure, 46 Allée d'Italie, 69364 Lyon Cédex 07, France1.
D000818:Animals; D015789:HLA-A2 Antigen / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology; D006508:Hepatitis Antibodies / Q000097:blood; D006526:Hepatitis C / Q000517:prevention & control; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D011995:Recombination, Genetic; D012672:Semliki forest virus / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D017778:Vaccines, Combined / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D015789:HLA-A2 Antigen; D006508:Hepatitis Antibodies; D017778:Vaccines, Combined; D019444:Vaccines, DNA; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases