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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.
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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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Publisher
MDPI
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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
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