title: Safety and Immunogenicity of a Recombinant Adenovirus Serotype 35-Vectored HIV-1 Vaccine in Adenovirus Serotype 5 Seronegative and Seropositive Individuals.
abstract: BACKGROUND
  Recombinant adenovirus serotype 5 (rAd5)-vectored HIV-1 vaccines have not prevented HIV-1 infection or disease and pre-existing Ad5 neutralizing antibodies may limit the clinical utility of Ad5 vectors globally. Using a rare Ad serotype vector, such as Ad35, may circumvent these issues, but there are few data on the safety and immunogenicity of rAd35 directly compared to rAd5 following human vaccination.
  
  
  METHODS
  HVTN 077 randomized 192 healthy, HIV-uninfected participants into one of four HIV-1 vaccine/placebo groups: rAd35/rAd5, DNA/rAd5, and DNA/rAd35 in Ad5-seronegative persons; and DNA/rAd35 in Ad5-seropositive persons. All vaccines encoded the HIV-1 EnvA antigen. Antibody and T-cell responses were measured 4 weeks post boost immunization.
  
  
  RESULTS
  All vaccines were generally well tolerated and similarly immunogenic. As compared to rAd5, rAd35 was equally potent in boosting HIV-1-specific humoral and cellular immunity and responses were not significantly attenuated in those with baseline Ad5 seropositivity. Like DNA, rAd35 efficiently primed rAd5 boosting. All vaccine regimens tested elicited cross-clade antibody responses, including Env V1/V2-specific IgG responses.
  
  
  CONCLUSIONS
  Vaccine antigen delivery by rAd35 is well-tolerated and immunogenic as a prime to rAd5 immunization and as a boost to prior DNA immunization with the homologous insert. Further development of rAd35-vectored prime-boost vaccine regimens is warranted.
authors.affiliation: Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA ; Department of Medicine, University of California, San Francisco, San Francisco, USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fuchs
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Bart
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Morgan
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Gilbert
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Kochar
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: DeRosa
authors.affiliation: Human Vaccine Institute, Duke University, Durham, NC, USA.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Population Health Division, San Francisco Department of Public Health, San Francisco, CA, USA.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Wagner
authors.affiliation: Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.affiliation: Laboratory of Infectious Disease Prevention, New York Blood Center, New York, NY, USA.
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.affiliation: The Hope Clinic, Division of Infectious Diseases, Emory University, Atlanta, GA, USA.
authors.forename: Nadine G
authors.initials: NG
authors.lastname: Rouphael
authors.affiliation: Infectious Diseases Division, Vanderbilt University School of Medicine, Nashville, TN, USA.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.affiliation: Division of Infectious Diseases, Columbia University College of Physicians and Surgeons, New York, NY, USA.
authors.forename: Magdalena E
authors.initials: ME
authors.lastname: Sobieszczyk
authors.affiliation: Fenway Health and the Division of Infectious Diseases, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, USA.
authors.forename: Kenneth H
authors.initials: KH
authors.lastname: Mayer
authors.affiliation: Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Edith
authors.initials: E
authors.lastname: Swann
authors.affiliation: Human Vaccine Institute, Duke University, Durham, NC, USA.
authors.forename: Hua-Xin
authors.initials: HX
authors.lastname: Liao
authors.affiliation: Human Vaccine Institute, Duke University, Durham, NC, USA.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, MD, USA.
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
keywords: Adenovirus 35; Adenovirus 5; DNA vaccine; HIV Vaccine; Randomized clinical trial