Volume 9 Supplement 2

AIDS Vaccine 2012

Open Access

Potent cellular immune responses after therapeutic immunization of HIV-positive patients with the PENNVAX®-B DNA vaccine in a Phase I Trial

  • P Tebas1,
  • L Ramirez1,
  • MP Morrow2,
  • J Yan2,
  • D Shah2,
  • J Lee2,
  • DB Weiner1,
  • J Boyer1,
  • M Bagarazzi2 and
  • NY Sardesai2
Retrovirology20129(Suppl 2):P276

DOI: 10.1186/1742-4690-9-S2-P276

Published: 13 September 2012

Background

Although highly active antiretroviral therapy (HAART) regimens have dramatically transformed treatment of HIV infection, achieving 95% adherence to HAART regimens is notoriously difficult. The successful creation of an immunotherapy for infection could eliminate the potential pitfalls associated with the necessity for long-term adherence to drug therapy. To that end, we evaluated the safety and immunogenicity of the PENNVAX®-B vaccine, delivered with in vivo electroporation (EP) in HIV-infected volunteers on HAART in a Phase I open-label study.

Methods

Enrollment criteria included HIV RNA<75copies/mL, CD4>400/µL with nadir >200/µL. Twelve eligible subjects received a 4 dose series (day 0, weeks 4, 8 and 16) of 3 mg PENNVAX®-B (consisting of SynCon® HIV Gag, Pol, and Env immunogens) intramuscularly followed by in vivo EP with the CELLECTRA®-5P device.

Results

All the enrolled subjects completed the immunization schedule. The vaccine demonstrated an acceptable safety profile and was generally well tolerated. Overall, 9 out of 12 subjects (75%) showed significant vaccine-specific T-cell responses in the form of IFN-γ ELISpot against at least one of the three vaccine antigens (Gag, Pol, or Env) following vaccination. Furthermore, responses were not dominated by a single antigen, as 50% of subjects had strong vaccine induced responses to at least 2 of the 3 antigens and 3 showed vaccine-induced responses to all 3 antigens. Importantly, the ELISpot responses induced by vaccination were predominantly CD8+T-cells, which are considered to be paramount in clearing chronic viral infections and an important measure of the performance of a therapeutic vaccine. Additionally, HIV-specific immune responses were assayed by flow cytometry to measure IFN-γ production by both CD4+ and CD8+T cells as well as co-expression of the CTL-related markers CD107a, GranzymeB and Perforin.

Conclusion

Analysis of these data should provide more definitive evidence of HIV-specific CTL function, which has been implicated in control of viral replication in HIV-infected patients.

Authors’ Affiliations

(1)
Department of Pathology and Laboratory Medicine, U of Pennsylvania
(2)
Inovio Pharmaceuticals

Copyright

© Tebas et al; licensee BioMed Central Ltd. 2012

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://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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