Skip to main content

Volume 6 Supplement 3

AIDS Vaccine 2009

OA05-06 LB. First-in-human Phase 1 safety and immunigenicity of an adenovirus serotype 26 HIV-1 vaccine vector

Background

Adenovirus serotype 26 (Ad26) is a rare Ad serotype that differs substantially from Ad5 in terms of baseline seroprevalence, receptor usage, tropism, innate immune profile, adaptive immune phenotype, and protective efficacy in the SIV/macaque model. Here we report the initial safety and immunogenicity assessment of a prototype Ad26 vector in humans.

Methods

Ad26 expressing the VRC EnvA test antigen was manufactured by Crucell. 36 Ad26 seronegative, healthy subjects were enrolled in a randomized, double-blinded, placebo-controlled, dose-escalation phase 1 study. Groups of 12 subjects received doses of 109, 1010, or 1011 vp of the Ad26-EnvA vector (N=10/group) or placebo (N=2/group) at weeks 0, 4, and 24. We performed a pre-specified blinded immunogenicity analysis after the first two immunizations. Validated IFN-gamma ELISPOT assays were performed with positivity criteria of >55 SFC/106 PBMC and >4-fold background.

Results

26/36 subjects were female, and 70/72 vaccinations were administered. Some reactogenicity was observed after the initial immunization in the highest dose group but typically resolved within 24 h. No vaccine-associated AEs or SAEs occurred. In all three dose groups, 2 subjects/group exhibited no detectable vector- or insert-specific immune responses at any timepoint, whereas 10 subjects/group developed positive Ad26 NAb titers, EnvA-specific ELISA titers, and EnvA-specific ELISPOT responses following vaccination. In the 109 vp dose group, the median ELISA titer was 1000 (IQR 300-3,000) and the median ELISPOT response was 381 SFC/106 PBMC (IQR 125-545) at week 8. In the 1011 vp dose group, the median ELISA titer was 5,477 (IQR 3,000-10,000) and the median ELISPOT response was 365 SFC/106 PBMC (IQR 85-715) at week 8.

Conclusion

The Ad26 vector is safe and immunogenic in humans at all three doses. Ad26 is therefore a promising new vector for further clinical studies to evaluate novel inserts such as mosaic HIV-1 Gag, Pol, Env antigens.

Author information

Affiliations

Authors

Corresponding author

Correspondence to LR Baden.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Baden, L., Dolin, R., O'Brien, K. et al. OA05-06 LB. First-in-human Phase 1 safety and immunigenicity of an adenovirus serotype 26 HIV-1 vaccine vector. Retrovirology 6, O36 (2009). https://doi.org/10.1186/1742-4690-6-S3-O36

Download citation

Keywords

  • ELISPOT Assay
  • Receptor Usage
  • Immune Phenotype
  • ELISA Titer
  • Adenovirus Serotype