Open Forum Infect Dis. 2015 Jun 5; 2(3):ofv082.

PubMed ID: 26199949

First-in-human evaluation of the safety and immunogenicity of a recombinant vesicular stomatitis virus (rVSV) HIV-1 gag vaccine (HVTN 090)

Fuchs JD, Frank I, Elizaga ML, Allen M, Frahm N, Kochar N, Li S, Edupuganti S, Kalams S, Tomaras G, Sheets R, Pensiero M, Tremblay M, Higgins T, Latham T, Egan M, Clarke D, Eldridge J, for the HVTN 090 Study Group and the NIAID HIV Vaccine Trials Network

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.