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Vaccine protection against murid herpesvirus‐4 is maintained when the priming virus lacks known latency genes
Author(s) -
Lawler Clara,
Simas João Pedro,
Stevenson Philip G
Publication year - 2020
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12299
Subject(s) - virology , biology , lytic cycle , latency (audio) , virus , virus latency , gene , epitope , viral replication , antibody , immunology , genetics , electrical engineering , engineering
γ‐Herpesviruses establish latent infections of lymphocytes and drive their proliferation, causing cancers and motivating a search for vaccines. Effective vaccination against murid herpesvirus‐4 (MuHV‐4)‐driven lymphoproliferation by latency‐impaired mutant viruses suggests that lytic access to the latency reservoir is a viable target for control. However, the vaccines retained the immunogenic Mu HV ‐4 M2 latency gene. Here, a strong reduction in challenge virus load was maintained when the challenge virus lacked the main latency‐associated CD 8 + T‐cell epitope of M2 , or when the vaccine virus lacked M2 entirely. This protection was maintained also when the vaccine virus lacked both episome maintenance and the genomic region encompassing M1 , M2 , M3 , M4 and ORF 4 . Therefore, protection did not require immunity to known Mu HV ‐4 latency genes. As the remaining vaccine virus genes have clear homologs in human γ‐herpesviruses, this approach of deleting viral latency genes could also be applied to them, to generate safe and effective vaccines against human disease.