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Stable Antigen is most effective for eliciting CD8 T-Cell responses after DNA vaccination and infection with recombinant Vaccinia Virus in vivo

Stable Antigen is most effective for eliciting CD8 T-Cell responses after DNA vaccination and infection with recombinant Vaccinia Virus in vivo

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SCHLIEHE, Christopher, Annegret BITZER, Marlies van den BROEK, Marcus GRÖTTRUP, 2012. Stable Antigen is most effective for eliciting CD8 T-Cell responses after DNA vaccination and infection with recombinant Vaccinia Virus in vivo. In: Journal of Virology. 86(18), pp. 9782-9793. ISSN 0022-538X. eISSN 1098-5514

@article{Schliehe2012Stabl-21998, title={Stable Antigen is most effective for eliciting CD8 T-Cell responses after DNA vaccination and infection with recombinant Vaccinia Virus in vivo}, year={2012}, doi={10.1128/JVI.00694-12}, number={18}, volume={86}, issn={0022-538X}, journal={Journal of Virology}, pages={9782--9793}, author={Schliehe, Christopher and Bitzer, Annegret and Broek, Marlies van den and Gröttrup, Marcus} }

eng deposit-license 2012 Journal of Virology ; 86 (2012), 18. - S. 9782-9793 Bitzer, Annegret 2013-03-06T15:41:04Z Broek, Marlies van den Broek, Marlies van den Gröttrup, Marcus Schliehe, Christopher Gröttrup, Marcus Bitzer, Annegret Schliehe, Christopher 2013-03-06T15:41:04Z The induction of strong CD8 T-cell responses against infectious diseases and cancer has remained a major challenge. Depending on the source of antigen and the infectious agent, priming of CD8 T cells requires direct and/or cross-presentation of antigenic peptides on major histocompatibility complex (MHC) class I molecules by professional antigen-presenting cells (APCs).<br />However, both pathways show distinct preferences concerning antigen stability. Whereas direct presentation was shown to efficiently present peptides derived from rapidly degraded proteins, cross-presentation is dependent on long-lived antigen species.<br />In this report, we analyzed the role of antigen stability on DNA vaccination and recombinant vaccinia virus (VV) infection using altered versions of the same antigen. The long-lived nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) can be targeted for degradation by N-terminal fusion to ubiquitin or, as we show here, to the ubiquitin-like modifier FAT10. Direct presentation by cells either transfected with NP-encoding plasmids or infected with recombinant VV in vitro was enhanced in the presence of short-lived antigens. In vivo, however, the highest induction of NP-specific CD8 T-cell responses was achieved in the presence of long-lived NP. Our experiments provide evidence that targeting antigens for proteasomal degradation does not improve the immunogenicity of DNA vaccines and recombinant VVs. Rather, it is the long-lived antigen that is superior for the efficient activation of MHC class I-restricted immune responses in vivo. Hence, our results suggest a dominant role for antigen cross-priming in DNA vaccination and recombinant VV infection. Stable Antigen is most effective for eliciting CD8 T-Cell responses after DNA vaccination and infection with recombinant Vaccinia Virus in vivo

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