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ORF6 and ORF61 Expressing MVA Vaccines Impair Early but Not Late Latency in Murine Gammaherpesvirus MHV-68 Infection. | LitMetric

AI Article Synopsis

  • - Gammaherpesviruses (γHV), such as Murine γHV 68 (MHV-68), pose significant health risks as they can cause long-lasting infections and lead to cancers in immunocompromised individuals.
  • - Researchers developed a modified vaccinia virus Ankara (recMVA) vaccine that targets specific MHV-68 antigens to enhance T cell responses, which are crucial for controlling the virus during both acute and latent phases of infection.
  • - While the recMVA vaccine effectively generated T cell responses and showed protective effects shortly after exposure to MHV-68, it was less effective in preventing long-term latency, indicating the need for further investigation into improving vaccine strategies focused on eliciting strong CD4

Article Abstract

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 . 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6930802PMC
http://dx.doi.org/10.3389/fimmu.2019.02984DOI Listing

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