First-in-human evaluation of the safety and immunogenicity of a recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001)

Abstract

Background. We report the first-in-human safety and immunogenicity assessment of a prototype Ad26 vector-based human immunodeficiency virus (HIV) vaccine in humans.Methods. Sixty Ad26-seronegative, healthy, HIV-uninfected subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Five groups of 12 subjects received 10 9-1011 vp of the Ad26-EnvA vaccine (N = 10/group) or placebo (N = 2/group) at weeks 0 and 24 or weeks 0, 4, and 24. Safety and immunogenicity were assessed.Results. Self-limited reactogenicity was observed after the initial immunization at the highest (1011 vp) dose. No product-related SAEs were observed. All subjects who received the Ad26-EnvA vaccine developed Ad26 NAb titers, EnvA-specific enzyme-linked immunosorbent assays (ELISA) titers, and EnvA-specific enzyme-linked immunospot assays (ELISPOT) responses. These responses persisted at week 52. At week 28 in the 109, 1010, 1011 vp 3-dose and the 10 10 and 5 × 1010 vp 2-dose groups, geometric mean EnvA ELISA titers were 6113, 12 470, 8545, 3470, and 9655 and mean EnvA ELISPOT responses were 397, 178, 736, 196, and 1311 SFC/106 peripheral blood mononuclear cells, respectively.Conclusion. This Ad26 vectored vaccine was generally safe and immunogenic at all doses tested. Reactogenicity was minimal with doses of 5 × 1010 vp or less. Ad26 is a promising new vaccine vector for HIV-1. © The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.