title: First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).
abstract: Background.  We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods.  Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 10(3) to 3.4 × 10(7) particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results.  Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions.  An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases.
authors.affiliation: San Francisco Department of Public Health, California ; University of California , San Francisco.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fuchs
authors.affiliation: University of Pennsylvania , Philadelphia.
authors.forename: Ian
authors.initials: I
authors.lastname: Frank
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Elizaga
authors.affiliation: Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland.
authors.forename: Mary
authors.initials: M
authors.lastname: Allen
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
authors.forename: Nicole
authors.initials: N
authors.lastname: Frahm
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention , Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Kochar
authors.affiliation: Statistical Center for HIV/AIDS Research and Prevention , Fred Hutchinson Cancer Research Center , Seattle, Washington.
authors.forename: Sue
authors.initials: S
authors.lastname: Li
authors.affiliation: Emory University , Atlanta, Georgia.
authors.forename: Srilatha
authors.initials: S
authors.lastname: Edupuganti
authors.affiliation: Vanderbilt University , Nashville, Tennessee.
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.affiliation: Duke Human Vaccine Institute, Duke University Medical Center , Durham, North Carolina.
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.affiliation: Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Sheets
authors.affiliation: Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland.
authors.forename: Michael
authors.initials: M
authors.lastname: Pensiero
authors.affiliation: Profectus Biosciences, Inc. , Tarrytown, New York.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Tremblay
authors.affiliation: Profectus Biosciences, Inc. , Tarrytown, New York.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Higgins
authors.affiliation: Profectus Biosciences, Inc. , Tarrytown, New York.
authors.forename: Theresa
authors.initials: T
authors.lastname: Latham
authors.affiliation: Profectus Biosciences, Inc. , Tarrytown, New York.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
authors.affiliation: Profectus Biosciences, Inc. , Tarrytown, New York.
authors.forename: David K
authors.initials: DK
authors.lastname: Clarke
authors.affiliation: Profectus Biosciences, Inc. , Tarrytown, New York.
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.forename: Mark
authors.initials: M
authors.lastname: Mulligan
authors.forename: Nadine
authors.initials: N
authors.lastname: Rouphael
authors.forename: Scharla
authors.initials: S
authors.lastname: Estep
authors.forename: Kyle
authors.initials: K
authors.lastname: Rybczyk
authors.forename: Deb
authors.initials: D
authors.lastname: Dunbar
authors.forename: Susan
authors.initials: S
authors.lastname: Buchbinder
authors.forename: Theresa
authors.initials: T
authors.lastname: Wagner
authors.forename: Reese
authors.initials: R
authors.lastname: Isbell
authors.forename: Victoria
authors.initials: V
authors.lastname: Chinnell
authors.forename: Jin
authors.initials: J
authors.lastname: Bae
authors.forename: Gina
authors.initials: G
authors.lastname: Escamilla
authors.forename: Jenny
authors.initials: J
authors.lastname: Tseng
authors.forename: Ramey
authors.initials: R
authors.lastname: Fair
authors.forename: Shelly
authors.initials: S
authors.lastname: Ramirez
authors.forename: Gail
authors.initials: G
authors.lastname: Broder
authors.forename: Liz
authors.initials: L
authors.lastname: Briesemeister
authors.forename: Adi
authors.initials: A
authors.lastname: Ferrara
keywords: HIV vaccine; dose-escalation; immunogenicity; safety; vesicular stomatitis virus