Recombinant BCG strains expressing the SIVmac251nef gene induce proliferative and CTL responses against nef synthetic peptides in mice.
CTL responses are known to be important for the control of HIV and SIV infections. Such responses are targeted against various components of these viruses including regulatory proteins like Nef. The SIVmac251nef gene was cloned in Mycobacterium bovis BCG under the control of P(AN), a promoter from Mycobacterium paratuberculosis. Nef was expressed as a fused polypeptide with ORF2, an open reading frame adjacent to P(AN). Mice inoculated with rBCG(SIVmac251nef) exhibited proliferative and CD8+ cytotoxic T-cell (CTL) responses against several Nef synthetic peptides. A mapping of the epitopes recognized by CTLs revealed that the central region of Nef is mainly involved in responses. This region had already been demonstrated to induce CTLs in experimentally SIV-infected macaques as well as in HIV-infected individuals. These results demonstrate the feasibility of constructing BCG vaccine strains expressing nef for eliciting cytotoxic responses.
Winter
N
N
Unité de Génétique Mycobactérienne (URA 1300 du CNRS), Institut Pasteur, Paris, France.
Lagranderie
M
M
Gangloff
S
S
Leclerc
C
C
Gheorghiu
M
M
Gicquel
B
B
D000818:Animals; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D003001:Cloning, Molecular; D000939:Epitopes / Q000276:immunology; D005260:Female; D015870:Gene Expression; D015693:Gene Products, nef / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D005814:Genes, Viral; D015754:Genes, nef; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*
D000939:Epitopes; D015693:Gene Products, nef; D011994:Recombinant Proteins; D014764:Viral Proteins