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dc.contributor.authorWang, Hong
dc.contributor.authorDavido, David J.
dc.contributor.authorMostafa, Heba H.
dc.contributor.authorMorrison, Lynda A.
dc.date.accessioned2022-07-05T18:47:35Z
dc.date.available2022-07-05T18:47:35Z
dc.date.issued2022-04-22
dc.identifier.citationWang, H.; Davido, D.J.; Mostafa, H.H.; Morrison, L.A. Efficacy of an HSV-1 NeuroAttenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication. Viruses 2022, 14, 869. https://doi.org/10.3390/v14050869en_US
dc.identifier.urihttp://hdl.handle.net/1808/32797
dc.description.abstractWe previously isolated an HSV-1 mutant, KOS-NA, that contains two non-synonymous mutations in UL39. One of the mutations, resulting in an R950H amino acid substitution in ICP6, renders KOS-NA severely neuro-attenuated and significantly reduces HSV-1 latency. Vaccination of mice with KOS-NA prior to corneal challenge provides significant protection against HSV-1-mediated eye diseases even at a very low immunizing dose, indicating its utility as a vaccine scaffold. Because KOS-NA contains a neuro-attenuating mutation in a single gene, we sought to improve its safety by deleting a portion of the UL29 gene whose protein product, ICP8, is essential for viral DNA replication. Whereas KOS-NA reduced replication of HSV-1 challenge virus in the corneal epithelium and protected mice against blepharitis and keratitis induced by the challenge virus, KOS-NA/8- and an ICP8- virus were significantly less efficacious except at higher doses. Our results suggest that the capacity to replicate, even at significantly reduced levels compared with wild-type HSV-1, may be an important feature of an effective vaccine. Means to improve safety of attenuated viruses as vaccines without compromising efficacy should be sought.en_US
dc.publisherMDPIen_US
dc.rightsThis is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectHerpes simplex virus 1en_US
dc.subjectVaccineen_US
dc.subjectCorneal infectionen_US
dc.subjectReplication-defectiveen_US
dc.titleEfficacy of an HSV-1 Neuro-Attenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replicationen_US
dc.typeArticleen_US
kusw.kuauthorDavido, David J.
kusw.kuauthorMostafa, Heba H.
kusw.kudepartmentMolecular Biosciencesen_US
dc.identifier.doi10.3390/v14050869en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC35632611en_US
dc.rights.accessrightsopenAccessen_US


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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Except where otherwise noted, this item's license is described as: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.