Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C.
Recombinants based on the attenuated vaccinia virus strains MVA and NYVAC are considered candidate vectors against different human diseases. In this study we have generated and characterized in BALB/c and in transgenic HHD mice the immunogenicity of two attenuated poxvirus vectors expressing in a single locus (TK) the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef (GPN) polyprotein of clade C (referred as MVA-C and NYVAC-C). In HHD mice primed with either MVA-C or NYVAC-C, or primed with DNA-C and boosted with the poxvirus vectors, the splenic T cell responses against clade C peptides spanning gp120/GPN was broad and mainly directed against Gag-1, Env-1 and Env-2 peptide pools. In BALB/c mice immunized with the homologous or the heterologous combination of poxvirus vectors or with Semliki forest virus (SFV) vectors expressing gp120/GPN, the immune response was also broad but the most immunogenic peptides were Env-1, GPN-1 and GPN-2. Differences in the magnitude of the cellular immune responses were observed between the poxvirus vectors depending on the protocol used. The specific cellular immune response triggered by the poxvirus vectors was Th1 type. The cellular response against the vectors was higher for NYVAC than for MVA in both HHD and BALB/c mice, but differences in viral antigen recognition between the vectors was observed in sera from the poxvirus-immunized animals. These results demonstrate the immunogenic potential of MVA-C and NYVAC-C as novel vaccine candidates against clade C of HIV-1.
Gómez
Carmen Elena
CE
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC, Ciudad Universitaria Cantoblanco, 28049 Madrid, Spain.
Nájera
Jose Luis
JL
Jiménez
Victoria
V
Bieler
Kurt
K
Wild
Jens
J
Kostic
Linda
L
Heidari
Shirin
S
Chen
Margaret
M
Frachette
Marie-Joelle
MJ
Pantaleo
Giuseppe
G
Wolf
Hans
H
Liljeström
Peter
P
Wagner
Ralf
R
Esteban
Mariano
M
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology; D015684:Gene Products, pol / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors; D015488:HIV Antigens / Q000235:genetics / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D023421:Models, Animal; D008969:Molecular Sequence Data; D012672:Semliki forest virus; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus; D014765:Viral Vaccines; D054311:nef Gene Products, Human Immunodeficiency Virus
D016915:AIDS Vaccines; D003062:Codon; D015683:Gene Products, gag; D015693:Gene Products, nef; D015684:Gene Products, pol; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; C078787:NYVAC vaccine; C572770:NYVAC-C vaccine; D019444:Vaccines, DNA; D014765:Viral Vaccines; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D007371:Interferon-gamma