Data_Sheet_1_ORF6 and ORF61 Expressing MVA Vaccines Impair Early but Not Late Latency in Murine Gammaherpesvirus MHV-68 Infection.pdf
Gammaherpesviruses (γHV) are important pathogens causing persistent infections which lead to several malignancies in immunocompromised patients. Murine γHV 68 (MHV-68), a homolog to human EBV and KSHV, has been employed as a classical pathogen to investigate the molecular pathogenicity of γHV infections. γHV 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-term latency at day 45. The data support further efforts aiming at improved vaccine development against γHV infections with special focus on targeting protective CD4+ T cell responses.
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References
- https://doi.org//10.1128/CMR.00044-10
- https://doi.org//10.1038/sj.jid.5700083
- https://doi.org//10.1016/j.canlet.2011.03.003
- https://doi.org//10.1016/S0140-6736(96)90989-7
- https://doi.org//10.1056/NEJM199505043321802
- https://doi.org//10.1126/science.7997879
- https://doi.org//10.1182/blood.V86.4.1276.bloodjournal8641276
- https://doi.org//10.4049/jimmunol.165.2.1074
- https://doi.org//10.1038/306480a0
- https://doi.org//10.1007/978-0-387-68945-6_28
- https://doi.org//10.1128/JVI.77.13.7696-7701.2003
- https://doi.org//10.1016/j.vaccine.2009.08.104
- https://doi.org//10.1128/JVI.01543-09
- https://doi.org//10.1128/JVI.78.19.10829-10832.2004
- https://doi.org//10.1128/JVI.75.17.8283-8288.2001
- https://doi.org//10.1099/vir.0.023085-0
- https://doi.org//10.1016/S0264-410X(98)00190-X
- https://doi.org//10.1128/JVI.02229-09
- https://doi.org//10.1099/0022-1317-73-9-2347
- https://doi.org//10.1128/JVI.77.4.2410-2417.2003
- https://doi.org//10.1016/S1357-4310(00)01813-X
- https://doi.org//10.1073/pnas.96.16.9281
- https://doi.org//10.1128/JVI.00237-06
- https://doi.org//10.4049/jimmunol.1302060
- https://doi.org//10.3390/v6072735
- https://doi.org//10.1016/j.vaccine.2013.03.020
- https://doi.org//10.1586/14760584.2013.845531
- https://doi.org//10.1016/j.jviromet.2010.04.012
- https://doi.org//10.1007/978-1-60761-652-8_30
- https://doi.org//10.1128/JVI.03244-14
- https://doi.org//10.1128/JVI.74.15.6964-6974.2000
- https://doi.org//10.1385/1-59259-789-0:077
- https://doi.org//10.1155/2012/472537
- https://doi.org//10.1371/journal.pone.0001638
- https://doi.org//10.1099/0022-1317-79-2-347
- https://doi.org//10.1084/jem.20070489
- https://doi.org//10.1128/JVI.00629-09
- https://doi.org//10.1128/JVI.01148-07
- https://doi.org//10.2144/000112096
- https://doi.org//10.1016/j.vaccine.2013.03.021
- https://doi.org//10.1128/JVI.00604-10
- https://doi.org//10.4049/jimmunol.170.7.3828
- https://doi.org//10.1099/0022-1317-77-11-2819
- https://doi.org//10.1128/JVI.00903-07
- https://doi.org//10.1016/j.cell.2015.08.004
- https://doi.org//10.1016/j.immuni.2017.01.003
- https://doi.org//10.1371/journal.ppat.1003129
- https://doi.org//10.1084/jem.20041912
- https://doi.org//10.2217/fmb.09.110
- https://doi.org//10.3390/vaccines2030581
- https://doi.org//10.1016/j.smim.2009.02.006
- https://doi.org//10.1056/NEJMoa1411627
- https://doi.org//10.1371/journal.pone.0118486
- https://doi.org//10.1128/IAI.00740-09
- https://doi.org//10.3390/v9100308
- https://doi.org//10.1099/0022-1317-77-4-627
- https://doi.org//10.1084/jem.184.3.863
- https://doi.org//10.1073/pnas.040575197
- https://doi.org//10.1038/nm1297-1346
- https://doi.org//10.1098/rstb.2000.0779
- https://doi.org//10.1146/annurev-immunol-072710-081639
- https://doi.org//10.1146/annurev-immunol-041015-055318
- https://doi.org//10.1016/j.cell.2015.10.054
- https://doi.org//10.3389/fimmu.2018.02569
- https://doi.org//10.1099/vir.0.19592-0
- https://doi.org//10.1099/vir.0.19760-0
- https://doi.org//10.1128/JVI.78.17.9215-9223.2004
- https://doi.org//10.1128/JVI.77.4.2522-2529.2003
- https://doi.org//10.1111/imcb.12299
- https://doi.org//10.1172/JCI125364
- https://doi.org//10.1016/j.vaccine.2015.11.062
- https://doi.org//10.1016/j.vaccine.2019.04.034
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Categories
- Transplantation Immunology
- Tumour Immunology
- Immunology not elsewhere classified
- Immunology
- Veterinary Immunology
- Animal Immunology
- Genetic Immunology
- Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies)
- Autoimmunity
- Cellular Immunology
- Humoural Immunology and Immunochemistry
- Immunogenetics (incl. Genetic Immunology)
- Innate Immunity