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Volume 6 Supplement 3

AIDS Vaccine 2009

P18-06. Increased HIV-specific immunity in HIV-infected individuals vaccinated with a DNA prime, rAd5 boost regimen

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Background

The Vaccine Research Center has developed a 3 DNA prime, recombinant adenovirus serotype 5 vector (rAd5) boost vaccination regimen that is immunogenic in HIV-uninfected individuals. Vaccination of HIV-infected individuals with potent immunogens offers the possibility of enhancing the magnitude, quality, and breadth of response compared to existing HIV immunity.

Methods

Seventeen HIV-infected men on HAART with undetectable viral loads (<50 copies/ml) and CD4+ T cells counts >350 cells/mm3 were enrolled in VRC 101. Eleven of 12 subjects randomized to the vaccination arm completed all immunizations; one did not receive the rAd5 boost. Four of 5 placebo recipients completed mock immunizations. Sixteen subjects completed 48 weeks of follow-up; 1 control subject discontinued after Week 36. Immunologic effects of vaccination were assessed based on the difference between pre-vaccination and 1 month post-rAd5 boost responses.

Results

Vaccination of HIV-infected individuals was well-tolerated; reactogenicity was similar to that seen in HIV-uninfected individuals. Viral loads remained undetectable in all but one vaccinee who showed transient low level virema (<100 copies/ml) during this study. No change in CD4+ T cell count was apparent in either controls or vaccinees. Vaccination induced significant increases in the frequency of IFN-gamma ELISpot response to Clade B Gag (P < 0.005), Pol (P < 0.05), and Clade A (P < 0.005), B (P < 0.005), and C Env (P < 0.05) overlapping 15 mer peptides. This increase was in part due to an increase in number of epitopes recognized. IFN-gamma ELISpot responses to Clade B Nef, not targeted by Ad5 boost vaccination, were not significantly increased in vaccinees. No significant change was observed in controls.

Conclusion

Pre-existing HIV-specific T cells responses can be safely boosted with existing vaccine products. The magnitude of these responses is large enough to allow the comparison of pre-existing responses to vaccine-induced responses at specific optimized epitopes and allow a systematic approach to the study of therapeutic vaccination in HIV-infected individuals.

Author information

Correspondence to JP Casazza.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Casazza, J., Bowman, K., Adzaku, S. et al. P18-06. Increased HIV-specific immunity in HIV-infected individuals vaccinated with a DNA prime, rAd5 boost regimen. Retrovirology 6, P315 (2009). https://doi.org/10.1186/1742-4690-6-S3-P315

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Keywords

  • Undetectable Viral Load
  • Boost Vaccination
  • Therapeutic Vaccination
  • Vaccination Regimen
  • Adenovirus Serotype