First-in-Human Evaluation of a Hexon Chimeric Adenovirus Vector Expressing HIV-1 Env (IPCAVD 002)
Year of Publication
Baden, LR; Walsh, SR; Seaman, MS; Johnson, JA; Tucker, RP; Kleinjan, JA; Gothing, JA; Engelson, BA; Carey, BR; Oza, A; Bajimaya, S; Peter, L; Bleckwehl, C; Abbink, P; Pau, MG; Weijtens, M; Kunchai, M; Swann, EM; Wolff, M; Dolin, R; Barouch, DH
J Infect Dis
Adenovirus 5 HVR48; Dose escalation; HIV Vaccine; Immunogenicity; safety
BACKGROUND: We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA. METHODS: Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 109 to 1011 viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. RESULTS: Self-limited reactogenicity was observed after the initial immunization in the highest (1011 vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 109, 1010, and 1011 vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5. CONCLUSIONS: Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions.