Lentiviral vectors encoding HIV-1 polyepitopes induce broad CTL responses in vivo.
Lentiviral vectors have been tested as vaccination vectors in anti-tumoral and anti-viral models. They efficiently transduce dendritic cells and stimulate strong T-cell responses against the encoded antigen. However, their capacity to stimulate a cytotoxic T-lymphocyte (CTL) response against several antigens has not been evaluated. Broad anti-human immunodeficiency virus 1 (HIV-1) T-cell immune responses are important for the control of HIV replication. We evaluated the potential of polyepitope-encoding lentiviral vectors to induce broad anti-HIV CTL responses. We constructed two lentiviral vectors coding for an HLA-A2- or HLA-B7-restricted polyepitope and evaluated their immunogenicity by direct injection of vector particles in HLA-A2 or HLA-B7 transgenic mice. In vitro cytotoxicity assays showed that a single immunization induces a strong, diversified, and long-lasting CTL response in both mouse models. CTL responses were directed against all 13 epitopes in the HLA-A2 system and 8 out of 12 in the HLA-B7 system. A second immunization augmented the number of responding mice in the HLA-A2 system but not in the HLA-B7 system. HLA-B7-immunized mice mounted strong interferon-gamma (IFN-gamma)-secreting T-cell responses against a majority of the epitopes and lysed peptide-loaded target cells in vivo. CTL responses in HLA-B7 mice were only partially dependent on CD4 T-cell help. This work underlines the potential of lentiviral vectors as candidates for therapeutic vaccination against acquired immunodeficiency syndrome.
Iglesias
Maria Candela
MC
Virologie Moléculaire et Vectorologie, Institut Pasteur, Paris, France.
Mollier
Karine
K
Beignon
Anne-Sophie
AS
Souque
Philippe
P
Adotevi
Olivier
O
Lemonnier
François
F
Charneau
Pierre
P
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology*; D015793:HLA-B7 Antigen / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D015793:HLA-B7 Antigen; D014764:Viral Proteins; D007371:Interferon-gamma