Format

Send to

Choose Destination
J Infect Dis. 2014 Oct 1;210(7):1052-61. doi: 10.1093/infdis/jiu217. Epub 2014 Apr 8.

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

Author information

1
Division of Infectious Diseases, Brigham and Women's Hospital Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts.
2
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts.
3
Division of Infectious Diseases, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts.
4
Division of Infectious Diseases, Brigham and Women's Hospital.
5
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center.
6
Crucell Holland BV, Leiden, the Netherlands.
7
EMMES Corporation, Rockville.
8
Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland.

Abstract

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.

KEYWORDS:

HIV vaccine; adenovirus 5 HVR48; dose escalation; immunogenicity; safety

PMID:
24719474
PMCID:
PMC4168302
DOI:
10.1093/infdis/jiu217
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center