title: A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects.
abstract: We evaluated replication-defective poxvirus vectors (modified vaccinia Ankara [MVA] and fowlpox [FPV]) in a homologous and heterologous vector prime-boost vaccination regimen containing matching HIV inserts (MVA-HIV and FPV-HIV) given at months 0, 1, 3, 5 and 7 in 150 healthy HIV-negative vaccinia-naïve participants. FPV-HIV alone was poorly immunogenic, while the high dose (10(9)pfu/2 ml) of MVA-HIV alone elicited maximal responses after two injections: CD4+ and CD8+ T-cell responses in 26/55 (47.3%) and 5/60 (8.3%) of participants, respectively, and IFN-γ ELISpot responses in 28/62 (45.2%). The infrequent CD8+ T-cell responses following MVA-HIV priming were boosted only by the heterologous (FPV-HIV) construct in 14/27 (51.9%) of participants post 4th vaccination. Alternatively, HIV envelope-specific binding antibodies were demonstrated in approximately two-thirds of recipients of the homologous boosting regimen, but in less than 20% of subjects after the heterologous vector boost. Thus, a heterologous poxvirus vector prime-boost regimen can induce HIV-specific CD8+ T-cell and CD4+ T-cell responses, which may be an important feature of an optimal regimen for preventive HIV vaccination.
authors.affiliation: Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. Michael Keefer@urmc.rochester.edu
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Marnie
authors.initials: M
authors.lastname: Elizaga
authors.forename: Barbara
authors.initials: B
authors.lastname: Metch
authors.forename: Stephen C
authors.initials: SC
authors.lastname: De Rosa
authors.forename: Paulo F
authors.initials: PF
authors.lastname: Barroso
authors.forename: Georgia
authors.initials: G
authors.lastname: Tomaras
authors.forename: Massimo
authors.initials: M
authors.lastname: Cardinali
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
authors.forename: Artur
authors.initials: A
authors.lastname: Kalichman
authors.forename: Valérie
authors.initials: V
authors.lastname: Philippon
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Olivier D
authors.initials: OD
authors.lastname: Defawe
authors.forename: Gail P
authors.initials: GP
authors.lastname: Mazzara
authors.forename: David
authors.initials: D
authors.lastname: Montefiori
authors.forename: Michael
authors.initials: M
authors.lastname: Pensiero
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Panicali
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004337:Drug Carriers; D005260:Female; D005587:Fowlpox virus / Q000235:genetics*; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D008297:Male; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D014616:Vaccinia virus / Q000235:genetics*; D055815:Young Adult
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D015483:HIV Antibodies