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OA04-03. Characterization of cell-mediated immune responses generated by recombinant modified vaccinia Ankara (rMVA)-HIV-1 in a phase I vaccine trial
Retrovirology volume 6, Article number: O27 (2009)
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.
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.
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.
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.
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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
- Cellular Immune Response
- Vaccination Strategy
- Vaccine Trial
- Vector Modality