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Orf Virus-Based Vaccine Vector D1701-V Induces Strong CD8+ T Cell Response against the Transgene but Not against ORFV-Derived Epitopes

Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany
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Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 295; https://doi.org/10.3390/vaccines8020295
Received: 14 May 2020 / Revised: 3 June 2020 / Accepted: 6 June 2020 / Published: 10 June 2020
(This article belongs to the Special Issue Reverse Vaccinology and Genomics)
The potency of viral vector-based vaccines depends on their ability to induce strong transgene-specific immune response without triggering anti-vector immunity. Previously, Orf virus (ORFV, Parapoxvirus) strain D1701-V was reported as a novel vector mediating protection against viral infections. The short-lived ORFV-specific immune response and the absence of virus neutralizing antibodies enables repeated immunizations and enhancement of humoral immune responses against the inserted antigens. However, only limited information exists about the D1701-V induced cellular immunity. In this study we employed major histocompatibility complex (MHC) ligandomics and immunogenicity analysis to identify ORFV-specific epitopes. Using liquid chromatography-tandem mass spectrometry we detected 36 ORFV-derived MHC I peptides, originating from various proteins. Stimulated splenocytes from ORFV-immunized mice did not exhibit specific CD8+ T cell responses against the tested peptides. In contrast, immunization with ovalbumin-expressing ORFV recombinant elicited strong SIINFEKL-specific CD8+ T lymphocyte response. In conclusion, our data indicate that cellular immunity to the ORFV vector is negligible, while strong CD8+ T cell response is induced against the inserted transgene. These results further emphasize the ORFV strain D1701-V as an attractive vector for vaccine development. Moreover, the presented experiments describe prerequisites for the selection of T cell epitopes exploitable for generation of ORFV-based vaccines by reverse genetics. View Full-Text
Keywords: Orf virus; ORFV; Parapoxvirus; viral vector; CD8+ T cells; epitopes; MHC class I; mass spectrometry; immunopeptidome; immune response; vaccine Orf virus; ORFV; Parapoxvirus; viral vector; CD8+ T cells; epitopes; MHC class I; mass spectrometry; immunopeptidome; immune response; vaccine
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Reguzova, A.; Ghosh, M.; Müller, M.; Rziha, H.-J.; Amann, R. Orf Virus-Based Vaccine Vector D1701-V Induces Strong CD8+ T Cell Response against the Transgene but Not against ORFV-Derived Epitopes. Vaccines 2020, 8, 295.

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