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

Publication Type
Journal Article
Year of Publication
Baden, Lindsey R; Walsh, Stephen R; Seaman, Michael S; Tucker, Robert P; Krause, Kathleen H; Patel, Alka; Johnson, Jennifer A; Kleinjan, Jane; Yanosick, Katherine E; Perry, James; Zablowsky, Elise; Abbink, Peter; Peter, Lauren; Iampietro, M Justin; Cheung, Ann; Pau, Maria G; Weijtens, Mo; Goudsmit, Jaap; Swann, Edith; Wolff, Mark; Loblein, Hayley; Dolin, Raphael; Barouch, Dan H
J Infect Dis
Date Published
2013 Jan 15
Adenoviruses, Human; AIDS Vaccines; Double-Blind Method; Female; Gene Products, env; HIV Antibodies; HIV Infections; HIV-1; Humans; Leukocytes, Mononuclear; Male; Treatment Outcome; Vaccines, Synthetic

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)-10(11) 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 (10(11) 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 10(9), 10(10), 10(11) vp 3-dose and the 10(10) and 5 × 10(10) 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/10(6) 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 × 10(10) vp or less. Ad26 is a promising new vaccine vector for HIV-1.