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Volume 6 Supplement 3

AIDS Vaccine 2009

P18-04. MVA-nef vaccination induces specific T-cell responses exerting functions associated with non-progressive disease in HIV-1 infected individuals

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Background

Modified vaccinia virus Ankara (MVA) vectored vaccines have been intensively investigated in several studies. In a therapeutic vaccination trial, we demonstrated that MVA expressing the HIV-1 protein Nef (MVA-nef) was safe in 10 HIV-1 infected individuals under ART and immunogenic in regard to the elicitation of IFN-γ mediated CD4 T-cell responses. Recent advancements in polychromatic flow-cytometry technology revealed that the sole evaluation of IFN-γ provides limited information about the quality of the immune response. In fact, simultaneous production of multiple cytokines by T-cells and a high proliferative capacity are associated with superior control of viral replication.

Methods

In a retrospective setting, we simultaneously assessed the expression of IFN-γ, IL-2, MIP-1β, CD154 and CD45RA in Nef-specific T-cell populations throughout the vaccination trial. Furthermore we applied a multi-colour CFSE based proliferation assay investigating the proliferative capacity and the simultaneous expression of IFN-γ, IL-2 and MIP-1β.

Results

Following MVA-nef vaccination, we observed a significant increase of polyfunctional Nef-specific CD4 T-cells, simultaneously expressing IFN-γ, IL-2 and CD154. Using the standard ICS no increase of Nef-specific CD8 T-cell responses was detected. However, by the CFSE based proliferation assay, we observed a clear expansion and a generally enhanced proliferative capacity of Nef-specific CD8 T-cells. Notably, MVA-nef induced increased IL-2 production by Nef-specific CD4 T-cells correlated with MVA-nef induced increased proliferative capacity of Nef-specific CD8 T-cells suggesting the possibility of a causal link between the two functions.

Conclusion

These results hold promise for the use of the poxvirus derived MVA-vector to stimulate potentially effective anti HIV T-cell responses and highlight the importance of sophisticated immunomonitoring tools to unravel concealed effects of immunologic interventions.

Author information

Correspondence to S Kutscher.

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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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Kutscher, S., Allgayer, S., Dembek, C. et al. P18-04. MVA-nef vaccination induces specific T-cell responses exerting functions associated with non-progressive disease in HIV-1 infected individuals. Retrovirology 6, P313 (2009). https://doi.org/10.1186/1742-4690-6-S3-P313

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Keywords

  • Vaccinia
  • Proliferative Capacity
  • Vaccination Trial
  • Therapeutic Vaccination
  • Modify Vaccinia Virus Ankara