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First-in-Human Evaluation of a Hexon Chimeric Adenovirus Vector Expressing HIV-1 Env (IPCAVD 002)


Journal Article

Baden, L.R.; , ; Seaman, M.S.; Johnson, J.A.; Tucker, R.P.; Kleinjan, J.A.; Gothing, J.A.; Engelson, B.A.; Carey, B.R.; Oza, A.; Bajimaya, S.; Peter, L.; Bleckwehl, C.; Abbink, P.; Pau, M.G.; Weijtens, M.; Kunchai, M.; Swann, E.M.; Wolff, M.; Dolin, R.; Barouch, D.H.

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.

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