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Efficacy of an HSV-1 Neuro-Attenuated Vaccine in Mice Is Reduced by Preventing Viral DNA Replication
Wang, Hong Davido, David J. Mostafa, Heba H. Morrison, Lynda A.
Wang, Hong
Davido, David J.
Mostafa, Heba H.
Morrison, Lynda A.
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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.
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Date
2022-04-22
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MDPI
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Wang_2022.pdf
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Keywords
Herpes simplex virus 1, Vaccine, Corneal infection, Replication-defective
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