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Volume 6 Supplement 3

AIDS Vaccine 2009

OA04-03. Characterization of cell-mediated immune responses generated by recombinant modified vaccinia Ankara (rMVA)-HIV-1 in a phase I vaccine trial

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Background

Potency of the cell-mediated immune response is now the critical metric for down-selection of candidate HIV-1 vaccines. Here we characterize the potency (magnitude and quality) of cell-mediated immunity generated in response to a multigenic rMVA-based HIV-1 (CRF01_AE-derived) vaccine.

Methods

49 healthy, vaccinia-naive volunteers were enrolled in a phase I randomized, double-blind, dose-escalation, route-comparison, placebo-controlled trial to assess the safety and immunogenicity of MVA-CMDR HIV-1 vaccine. The study was divided into Part A: low-dose 106/pfu ID versus 107 pfu/IM and Part B: high-dose 107 pfu/ID vs 108 pfu/IM. Vaccinations were given at months 0, 1 and 3 with an active:placebo ratio of 10:2. Chromium-release CTL, IFNγ Elispot, and polyfunctional flow cytometry (IL-2/IFNγ/TNFα/MIP-1β/CD107a), were performed on all volunteers. Synthetic peptide pools and GLP-grade MVA were used to assess insert (Gag/Pol/Env) and vector immunogenicity respectively.

Results

Vector-specific responses were robust (> 80% response rate at high-dose), durable (maintained at least 6 months), and exhibited a dose-dependent increase in both magnitude and response rate among the 4 arms of the trial. HIV-insert-specific responses were detected using all assay platforms, but were lower than the vector-specific responses in both magnitude and response rate in all arms of the trial (~60% at high-dose by CTL, Elispot and ICS assays). Specifically, polyfunctional analysis revealed a TNFα/IL-2/IFNγ bias in CD4+ T cells and a MIP-1β/CD107a/IFNγ bias in CD8+ T cells, with CD4+ T cell responses more frequent than CD8+ T cell responses to the HIV inserts. Vector-specific immune responses showed a boosting effect from the 2nd to the 3rd immunization.

Conclusion

rMVA vaccination induces a dose-dependent, robust and durable polyfunctional cellular immune response as measured by IFNγ Elispot, CTL and intracellular cytokine stimulation assays. Although vector-specific responses tend to dominate over insert-specific responses, the data supports further exploration of MVA as a vector modality in prime-boost vaccination strategies.

Author information

Correspondence to JR Currier.

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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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Currier, J., De Souza, M., Ratto-Kim, S. et al. OA04-03. Characterization of cell-mediated immune responses generated by recombinant modified vaccinia Ankara (rMVA)-HIV-1 in a phase I vaccine trial. Retrovirology 6, O27 (2009). https://doi.org/10.1186/1742-4690-6-S3-O27

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Keywords

  • Cellular Immune Response
  • Vaccinia
  • Vaccination Strategy
  • Vaccine Trial
  • Vector Modality