advanced search

<< Back To Home

FIRST-IN-HUMAN EVALUATION OF THE SAFETY AND IMMUNOGENICITY OF A RECOMBINANT VESICULAR STOMATITIS VIRUS HUMAN IMMUNODEFICIENCY VIRUS-1 gag VACCINE (HVTN 090)

Monday, 13th of July 2015

FIRST-IN-HUMAN EVALUATION OF THE SAFETY AND IMMUNOGENICITY OF A RECOMBINANT VESICULAR STOMATITIS VIRUS HUMAN IMMUNODEFICIENCY VIRUS-1 gag VACCINE (HVTN 090)

1. Jonathan D. Fuchs1,2, Ian Frank3, Marnie L. Elizaga4, Mary Allen6, Nicole Frahm4, Nidhi Kochar5, Sue Li5, Srilatha Edupuganti7, Spyros A. Kalams8, Georgia D. Tomaras9, Rebecca Sheets6, Michael Pensiero6, Marc A. Tremblay10, Terry J. Higgins10, Theresa Latham10, Michael A. Egan10, David K. Clarke10 and John H. Eldridge10

for the HVTN 090 Study Group and the National Institutes of Allergy and Infectious Diseases HIV Vaccine Trials Network

+ Author Affiliations

1.      ¹San Francisco Department of Public Health, California

2.      ²University of California, San Francisco

3.      ³University of Pennsylvania, Philadelphia

4.      ⁴Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center

5.      ⁵Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington

6.      ⁶Division of AIDS, National Institutes of Allergy and Infectious Diseases, Bethesda, Maryland

7.      ⁷Emory University, Atlanta, Georgia

8.      ⁸Vanderbilt University, Nashville, Tennessee

9.      ⁹Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina

10.  ¹⁰Profectus Biosciences, Inc., Tarrytown, New York

1. Correspondence: Jonathan D. Fuchs, MD, MPH, San Francisco Department of Public Health, 25 Van Ness Ave, Suite 500, San Francisco, CA 94102 (jonathan.fuchs@sfdph.org).

1. Presented in part: AIDS Vaccine Conference, September 2013, Barcelona, Spain; Keystone Symposium, HIV Vaccines, March 2014, Banff, Canada.

• Received April 7, 2015.
• Accepted June 1, 2015.

Abstract below; full text is at http://ofid.oxfordjournals.org/content/2/3/ofv082.full.pdf+html

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 × 10³ to 3.4 × 10⁷ 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.