title: An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses.
abstract: The EuroVacc 02 phase I trial has evaluated the safety and immunogenicity of a prime-boost regimen comprising recombinant DNA and the poxvirus vector NYVAC, both expressing a common immunogen consisting of Env, Gag, Pol, and Nef polypeptide domain from human immunodeficiency virus (HIV)-1 clade C isolate, CN54. 40 volunteers were randomized to receive DNA C or nothing on day 0 and at week 4, followed by NYVAC C at weeks 20 and 24. The primary immunogenicity endpoints were measured at weeks 26 and 28 by the quantification of T cell responses using the interferon gamma enzyme-linked immunospot assay. Our results indicate that the DNA C plus NYVAC C vaccine regimen was highly immunogenic, as indicated by the detection of T cell responses in 90% of vaccinees and was superior to responses induced by NYVAC C alone (33% of responders). The vaccine-induced T cell responses were (a) vigorous in the case of the env response (mean 480 spot-forming units/10(6) mononuclear cells at weeks 26/28), (b) polyfunctional for both CD4 and CD8 T cell responses, (c) broad (the average number of epitopes was 4.2 per responder), and (d) durable (T cell responses were present in 70% of vaccinees at week 72). The vaccine-induced T cell responses were strongest and most frequently directed against Env (91% of vaccines), but smaller responses against Gag-Pol-Nef were also observed in 48% of vaccinees. These results support the development of the poxvirus platform in the HIV vaccine field and the further clinical development of the DNA C plus NYVAC C vaccine regimen.
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Centre Hospitalier Universitaire Vaudois, University of Lausanne, 1011 Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stöhr
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Tapia
authors.forename: Miguel
authors.initials: M
authors.lastname: Garcia
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Medjitna-Rais
authors.forename: Séverine
authors.initials: S
authors.lastname: Burnet
authors.forename: Cristina
authors.initials: C
authors.lastname: Cellerai
authors.forename: Otto
authors.initials: O
authors.lastname: Erlwein
authors.forename: Tristan
authors.initials: T
authors.lastname: Barber
authors.forename: Christiane
authors.initials: C
authors.lastname: Moog
authors.forename: Peter
authors.initials: P
authors.lastname: Liljestrom
authors.forename: Ralf
authors.initials: R
authors.lastname: Wagner
authors.forename: Hans
authors.initials: H
authors.lastname: Wolf
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kraehenbuhl
authors.forename: Mariano
authors.initials: M
authors.lastname: Esteban
authors.forename: Jonathan
authors.initials: J
authors.lastname: Heeney
authors.forename: Marie-Joelle
authors.initials: MJ
authors.lastname: Frachette
authors.forename: James
authors.initials: J
authors.lastname: Tartaglia
authors.forename: Sheena
authors.initials: S
authors.lastname: McCormack
authors.forename: Abdel
authors.initials: A
authors.lastname: Babiker
authors.forename: Jonathan
authors.initials: J
authors.lastname: Weber
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
mesh_terms: D016915:AIDS Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D003062:Codon; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D018604:Epitope Mapping; D006801:Humans; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D014612:Vaccines; D014765:Viral Vaccines / Q000737:chemistry / Q000627:therapeutic use*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D016915:AIDS Vaccines; D003062:Codon; C078787:NYVAC vaccine; D010455:Peptides; D014612:Vaccines; D014765:Viral Vaccines; D054299:env Gene Products, Human Immunodeficiency Virus; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus