| Autor: |
Fuchs JD; San Francisco Department of Public Health, California ; University of California , San Francisco., Frank I; University of Pennsylvania , Philadelphia., Elizaga ML; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center., Allen M; Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland., Frahm N; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center., Kochar N; Statistical Center for HIV/AIDS Research and Prevention , Fred Hutchinson Cancer Research Center , Seattle, Washington., Li S; Statistical Center for HIV/AIDS Research and Prevention , Fred Hutchinson Cancer Research Center , Seattle, Washington., Edupuganti S; Emory University , Atlanta, Georgia., Kalams SA; Vanderbilt University , Nashville, Tennessee., Tomaras GD; Duke Human Vaccine Institute, Duke University Medical Center , Durham, North Carolina., Sheets R; Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland., Pensiero M; Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland., Tremblay MA; Profectus Biosciences, Inc. , Tarrytown, New York., Higgins TJ; Profectus Biosciences, Inc. , Tarrytown, New York., Latham T; Profectus Biosciences, Inc. , Tarrytown, New York., Egan MA; Profectus Biosciences, Inc. , Tarrytown, New York., Clarke DK; Profectus Biosciences, Inc. , Tarrytown, New York., Eldridge JH; Profectus Biosciences, Inc. , Tarrytown, New York., Mulligan M, Rouphael N, Estep S, Rybczyk K, Dunbar D, Buchbinder S, Wagner T, Isbell R, Chinnell V, Bae J, Escamilla G, Tseng J, Fair R, Ramirez S, Broder G, Briesemeister L, Ferrara A |
| Abstrakt: |
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. |
