title: Head-to-Head Comparison of Poxvirus NYVAC and ALVAC Vectors Expressing Identical HIV-1 Clade C Immunogens in Prime-Boost Combination with Env Protein in Nonhuman Primates.
abstract: We compared the HIV-1-specific cellular and humoral immune responses elicited in rhesus macaques immunized with two poxvirus vectors (NYVAC and ALVAC) expressing the same HIV-1 antigens from clade C, Env gp140 as a trimeric cell-released protein and a Gag-Pol-Nef polyprotein as Gag-induced virus-like particles (VLPs) (referred to as NYVAC-C and ALVAC-C). The immunization protocol consisted of two doses of the corresponding poxvirus vector plus two doses of a combination of the poxvirus vector and a purified HIV-1 gp120 protein from clade C. This immunogenicity profile was also compared to that elicited by vaccine regimens consisting of two doses of the ALVAC vector expressing HIV-1 antigens from clades B/E (ALVAC-vCP1521) plus two doses of a combination of ALVAC-vCP1521 and HIV-1 gp120 protein from clades B/E (similar to the RV144 trial regimen) or clade C. The results showed that immunization of macaques with NYVAC-C stimulated at different times more potent HIV-1-specific CD4(+) T-cell responses and induced a trend toward higher-magnitude HIV-1-specific CD8(+) T-cell immune responses than did ALVAC-C. Furthermore, NYVAC-C induced a trend toward higher levels of binding IgG antibodies against clade C HIV-1 gp140, gp120, or murine leukemia virus (MuLV) gp70-scaffolded V1/V2 and toward best cross-clade-binding IgG responses against HIV-1 gp140 from clades A, B, and group M consensus, than did ALVAC-C. Of the linear binding IgG responses, most were directed against the V3 loop in all immunization groups. Additionally, NYVAC-C and ALVAC-C also induced similar levels of HIV-1-neutralizing antibodies and antibody-dependent cellular cytotoxicity (ADCC) responses. Interestingly, binding IgA antibody levels against HIV-1 gp120 or MuLV gp70-scaffolded V1/V2 were absent or very low in all immunization groups. Overall, these results provide a comprehensive survey of the immunogenicity of NYVAC versus ALVAC expressing HIV-1 antigens in nonhuman primates and indicate that NYVAC may represent an alternative candidate to ALVAC in the development of a future HIV-1 vaccine.
  
  
  OBJECTIVE
  The finding of a safe and effective HIV/AIDS vaccine immunogen is one of the main research priorities. Here, we generated two poxvirus-based HIV vaccine candidates (NYVAC and ALVAC vectors) expressing the same clade C HIV-1 antigens in separate vectors, and we analyzed in nonhuman primates their immunogenicity profiles. The results showed that immunization with NYVAC-C induced a trend toward higher HIV-1-specific cellular and humoral immune responses than did ALVAC-C, indicating that this new NYVAC vector could be a novel optimized HIV/AIDS vaccine candidate for human clinical trials.
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: García-Arriaza
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Perdiguero
authors.affiliation: Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Seaman
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Celia
authors.initials: C
authors.lastname: Labranche
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Yates
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Shen
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Duke University, Durham, North Carolina, USA.
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Foulds
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Adrian
authors.initials: A
authors.lastname: McDermott
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Shing-Fen
authors.initials: SF
authors.lastname: Kao
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Roederer
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Natalie
authors.initials: N
authors.lastname: Hawkins
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Self
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
authors.forename: Jiansheng
authors.initials: J
authors.lastname: Yao
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Farrell
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Phogat
authors.affiliation: Sanofi Pasteur, Swiftwater, Pennsylvania, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Tartaglia
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, Massachusetts, USA.
authors.forename: Susan W
authors.initials: SW
authors.lastname: Barnett
authors.affiliation: Novartis Vaccines and Diagnostics, Inc., Cambridge, Massachusetts, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Burke
authors.affiliation: Advanced BioScience Laboratories, Inc., Kensington, Maryland, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Cristillo
authors.affiliation: Advanced BioScience Laboratories, Inc., Kensington, Maryland, USA.
authors.forename: Deborah
authors.initials: D
authors.lastname: Weiss
authors.affiliation: Global Solutions for Infectious Diseases, San Francisco, California, USA.
authors.forename: Carter
authors.initials: C
authors.lastname: Lee
authors.affiliation: The Biodesign Institute at Arizona State University, Tempe, Arizona, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Kibler
authors.affiliation: The Biodesign Institute at Arizona State University, Tempe, Arizona, USA.
authors.forename: Bert
authors.initials: B
authors.lastname: Jacobs
authors.affiliation: University of Regensburg, Regensburg, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Asbach
authors.affiliation: University of Regensburg, Regensburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.affiliation: EuroVacc Foundation, Lausanne, Switzerland.
authors.forename: Song
authors.initials: S
authors.lastname: Ding
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.affiliation: Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Madrid, Spain mesteban@cnb.csic.es.
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing; D002642:Chick Embryo; D015686:Gene Products, env / Q000378:metabolism*; D005822:Genetic Vectors / Q000276:immunology*; D015483:HIV Antibodies; D015488:HIV Antigens / Q000378:metabolism; D015658:HIV Infections / Q000517:prevention & control*; D008253:Macaca mulatta; D011212:Poxviridae / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014614:Vaccines, Synthetic / Q000276:immunology*; D010948:Viral Plaque Assay; D014765:Viral Vaccines / Q000276:immunology*
chemical_list: D016915:AIDS Vaccines; C078788:ALVAC vaccine; D057134:Antibodies, Neutralizing; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; C572770:NYVAC-C vaccine; D014614:Vaccines, Synthetic; D014765:Viral Vaccines