First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002).

Publication Type
Journal Article
Year of Publication
Baden, Lindsey R; Walsh, Stephen R; Seaman, Michael S; Johnson, Jennifer A; Tucker, Robert P; Kleinjan, Jane A; Gothing, Jon A; Engelson, Brian A; Carey, Brittany R; Oza, Avinash; Bajimaya, Shringkhala; Peter, Lauren; Bleckwehl, Chelsea; Abbink, Peter; Pau, Maria G; Weijtens, Mo; Kunchai, Meghan; Swann, Edith M; Wolff, Mark; Dolin, Raphael; Barouch, Dan H
J Infect Dis
Date Published
2014 Oct 01
Adenoviruses, Human; Adolescent; Adult; AIDS Vaccines; Antibodies, Neutralizing; Capsid Proteins; Double-Blind Method; Drug Carriers; Drug-Related Side Effects and Adverse Reactions; env Gene Products, Human Immunodeficiency Virus; Enzyme-Linked Immunosorbent Assay; Enzyme-Linked Immunospot Assay; Female; Gene Expression; Genetic Vectors; HIV Antibodies; HIV-1; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Placebos; Vaccines, Synthetic; Young Adult

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 10(9) to 10(11) 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 (10(11) 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 10(9), 10(10), and 10(11) 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. Clinical Trials Registration. NCT00695877.