Head-to-head comparison on the immunogenicity of two HIV/AIDS vaccine candidates based on the attenuated poxvirus strains MVA and NYVAC co-expressing in a single locus the HIV-1BX08 gp120 and HIV-1(IIIB) Gag-Pol-Nef proteins of clade B.
In this investigation we have generated and defined the immunogenicity of two novel HIV/AIDS vaccine candidates based on the highly attenuated vaccinia virus strains, MVA and NYVAC, efficiently expressing in the same locus (TK) and under the same viral promoter the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef antigens of clade B (referred as MVA-B and NYVAC-B). In infected human HeLa cells, gp120 is released from cells and GPN is produced as a polyprotein; NYVAC-B induces severe apoptosis but not MVA-B. The two poxvirus vectors showed genetic stability of the inserts. In BALB/c and in transgenic HHD mice for human HLA-A2 class I, both vectors are efficient immunogens and induced broad cellular immune responses against peptides represented in the four HIV-1 antigens. Some differences were observed in the magnitude and breadth of the immune response in the mouse models. In DNA prime/poxvirus boost protocols, the strongest immune response, as measured by fresh IFN-gamma and IL-2 ELISPOT, was obtained in BALB/c mice boosted with NYVAC-B, while in HHD mice there were no differences between the poxvirus vectors. When the prime/boost was performed with homologous or with combination of poxvirus vectors, the protocols MVA-B/MVA-B and NYVAC-B/NYVAC-B, or the combination NYVAC-B/MVA-B gave the most consistent broader immune response in both mouse models, although the magnitude of the overall response was higher for the DNA-B/poxvirus-B regime. All of the immunization protocols induced some humoral response against the gp160 protein from HIV-1 clone LAV. Our findings indicate that MVA-B and NYVAC-B meet the criteria to be potentially useful vaccine candidates against HIV/AIDS.
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
Eva Pérez
EP
Jiménez
Victoria
V
Wagner
Ralf
R
Graf
Marcus
M
Frachette
Marie-Joelle
MJ
Liljeström
Peter
P
Pantaleo
Giuseppe
G
Esteban
Mariano
M
D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology; D001483:Base Sequence; D002642:Chick Embryo; D015685:Fusion Proteins, gag-pol / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015693:Gene Products, nef / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D042822:Genomic Instability; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction / Q000379:methods; D011212:Poxviridae / Q000235:genetics / Q000276:immunology; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D000956:Antigens, Viral; D015685:Fusion Proteins, gag-pol; D015693:Gene Products, nef; D015699:HIV Envelope Protein gp120; C082068:HIV-1 IIIB gp120 subunit vaccine; D015789:HLA-A2 Antigen; C078787:NYVAC vaccine; D014613:Vaccines, Attenuated; D014765:Viral Vaccines