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)-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.

Clinical trials registration: NCT00618605.

Figure 1.

Ad26 neutralizing antibody responses by group. Individual Ad26 neutralizing antibody responses from subjects by week and vaccine group are shown. Dots show individual responses at a given time point. Red horizontal lines show the median values at a given time point for the group. Red arrows show times when vaccine or placebo was administered (the week 4 placebo injection was not given in groups 4 and 5).

Figure 2.

EnvA enzyme-linked immunosorbent assays (ELISA) responses by group. Individual EnvA ELISA responses from subjects by week and vaccine group are shown. Dots show individual responses at a given time point. Red horizontal lines show the median values at a given time point for the group. Red arrows show times when vaccine or placebo was administered (the week 4 placebo injection was not given in groups 4 and 5).

Figure 3.

EnvA enzyme-linked immunospot assays (ELISPOT) responses by group. Individual EnvA ELISPOT responses from subjects by week and vaccine group are shown. Dots show individual responses at a given time point. Red horizontal lines show the median values at a given time point for the group. Red arrows show times when vaccine or placebo was administered (the week 4 placebo injection was not given in groups 4 and 5). Abbreviations: PBMC, peripheral blood mononuclear cell; SFC, spot-forming cell.