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

JD Fuchs, I Frank, ML Elizaga, M Allen… - Open forum …, 2015 - academic.oup.com
JD Fuchs, I Frank, ML Elizaga, M Allen, N Frahm, N Kochar, S Li, S Edupuganti, SA Kalams
Open forum infectious diseases, 2015academic.oup.com
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 …
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 × 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.
Oxford University Press