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Open Forum Infect Dis. 2015 Jun 5;2(3):ofv082. doi: 10.1093/ofid/ofv082. eCollection 2015 Sep.

First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090).

Author information

1
San Francisco Department of Public Health, California ; University of California , San Francisco.
2
University of Pennsylvania , Philadelphia.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center.
4
Division of AIDS, National Institutes of Allergy and Infectious Diseases , Bethesda, Maryland.
5
Statistical Center for HIV/AIDS Research and Prevention , Fred Hutchinson Cancer Research Center , Seattle, Washington.
6
Emory University , Atlanta, Georgia.
7
Vanderbilt University , Nashville, Tennessee.
8
Duke Human Vaccine Institute, Duke University Medical Center , Durham, North Carolina.
9
Profectus Biosciences, Inc. , Tarrytown, New York.

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.

KEYWORDS:

HIV vaccine; dose-escalation; immunogenicity; safety; vesicular stomatitis virus

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