PuSH - Publication Server of Helmholtz Zentrum München: ORF6 and ORF61 expressing MVA vaccines impair early but not late latency in murine gammaherpesvirus MHV-68 infection.

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Samreen, B.* ; Tao, S.* ; Tischer, K.* ; Adler, H. ; Drexler, I.*

ORF6 and ORF61 expressing MVA vaccines impair early but not late latency in murine gammaherpesvirus MHV-68 infection.

Front. Immunol. 10:2984 (2019)

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Gammaherpesviruses (gamma HV) are important pathogens causing persistent infections which lead to several malignancies in immunocompromised patients. Murine gamma HV 68 (MHV-68), a homolog to human EBV and KSHV, has been employed as a classical pathogen to investigate the molecular pathogenicity of gamma HV infections. gamma HV express distinct antigens during lytic or latent infection and antigen-specific T cells have a significant role in controlling the acute and latent viral infection, although the quality of anti-viral T cell responses required for protective immunity is not well-understood. We have generated recombinant modified vaccinia virus Ankara (recMVA) vaccines via MVA-BAC homologous recombination technology expressing MHV-68 ORF6 and ORF61 antigens encoding both MHC class I and II-restricted epitopes. After vaccination, we examined T cell responses before and after MHV-68 infection to determine their involvement in latent virus control. We show recognition of recMVA- and MHV-68-infected APC by ORF6 and ORF61 epitope-specific T cell lines in vitro. The recMVA vaccines efficiently induced MHV-68-specific CD8+ and CD4+ T cell responses after a single immunization and more pronounced after homologous prime/boost vaccination in mice. Moreover, we exhibit protective capacity of prophylactic recMVA vaccination during early latency at day 17 after intranasal challenge with MHV-68, but failed to protect from latency at day 45. Further T cell analysis indicated that T cell exhaustion was not responsible for the lack of protection by recMVA vaccination in long-termlatency at day 45. The data support further efforts aiming at improved vaccine development against gamma HV infections with special focus on targeting protective CD4+ T cell responses.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Vaccinia Virus ; Mva ; T Cell Response ; Viral Vector Vaccine ; Mhv-68 ; Gammaherpesvirus; Epstein-barr-virus; Cd8(+) T-cells; Artificial Chromosome Clone; Gamma-herpesvirus; Dna-sequences; Antibody-responses; Dendritic Cells; B-cells; Vaccination; Deficient

ISSN (print) / ISBN 1664-3224

e-ISSN 1664-3224

Journal Frontiers in Immunology

Quellenangaben Volume: 10, Article Number: 2984

Publisher Frontiers

Publishing Place Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Research Unit Lung Repair and Regeneration (LRR)

Grants MOI II Graduate School
DAAD
DFG