The HIV-1 chimeric protein CR3 expressed by poxviral vectors induces a diverse CD8+ T cell response in mice and is antigenic for PBMCs from HIV+ patients.
Recombinant avipoxvirus vectors are attractive for vaccination against human immunodeficiency virus type 1 (HIV-1), where induction of a cytotoxic CD8(+) T cell (CTL) response seems to be an important component of protective immunity. We expressed the chimeric protein CR3, composed by CTL epitopes rich regions from, RT, Gag and Nef and conserved Th cell epitopes from gp120, gp41 and Vpr of HIV-1 in a fowlpox virus (FWPV) vector (FPCR3), and used this vector to induce HIV-specific CTL responses in mice. Mice immunised twice intraperitoneally with FPCR3, developed a CD8(+) T cell response measured as production of IFN-gamma by splenocytes in response to stimulation with P815 cells infected with recombinant vaccinia viruses (rVV) expressing CR3, Gag and Nef. The number of IFN-gamma secreting cells was markedly higher when a P815 cell line constitutively expressing CR3 was used as target cells for Enzyme-linked-immunospot (ELISPOT). CR3 epitopes were also specifically recognised by human PBMCs from three HIV(+) patients with different haplotypes. These results confirm the potential of FWPV vectors expressing these novel HIV-1 chimeric proteins to induce a simultaneous CD8(+) T cell response against conserved viral targets and early expressed regulatory proteins.
Vázquez-Blomquist
Dania
D
Departamento de SIDA, División de Vacunas, Centro de Ingeniería Genética y Biotecnología, Apdo 6162, Cubanacan, Playa, 10600, Ciudad Habana, Cuba.
Iglesias
Enrique
E
González-Horta
Eddy E
EE
Duarte
Carlos A
CA
D000818:Animals; D000918:Antibody Specificity; D018150:Avipoxvirus / Q000235:genetics*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D003001:Cloning, Molecular; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D016177:Macrophage-1 Antigen / Q000096:biosynthesis* / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology; D014764:Viral Proteins / Q000276:immunology
D000939:Epitopes; D016177:Macrophage-1 Antigen; D011993:Recombinant Fusion Proteins; D014764:Viral Proteins