dc.contributor.author | Wang, Hong | |
dc.contributor.author | Davido, David J. | |
dc.contributor.author | Mostafa, Heba H. | |
dc.contributor.author | Morrison, Lynda A. | |
dc.date.accessioned | 2022-07-05T18:47:35Z | |
dc.date.available | 2022-07-05T18:47:35Z | |
dc.date.issued | 2022-04-22 | |
dc.identifier.citation | Wang, 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/v14050869 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32797 | |
dc.description.abstract | We 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.publisher | MDPI | en_US |
dc.rights | 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. | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en_US |
dc.subject | Herpes simplex virus 1 | en_US |
dc.subject | Vaccine | en_US |
dc.subject | Corneal infection | en_US |
dc.subject | Replication-defective | en_US |
dc.title | Efficacy of an HSV-1 Neuro-Attenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Davido, David J. | |
kusw.kuauthor | Mostafa, Heba H. | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.3390/v14050869 | en_US |
kusw.oaversion | Scholarly/refereed, publisher version | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC35632611 | en_US |
dc.rights.accessrights | openAccess | en_US |