Distinguishing Features of High- and Low-Dose Vaccine against Ocular HSV-1 Infection Correlates with Recognition of Specific HSV-1-Encoded Proteins.

Autor:	Carr DJJ; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; dan-carr@ouhsc.edu.; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104; and., Gmyrek GB; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104., Filiberti A; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104., Berube AN; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104., Browne WP; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104., Gudgel BM; Department of Ophthalmology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104., Sjoelund VH; Laboratory for Molecular Biology and Cytometry Research, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104.
Jazyk:	angličtina
Zdroj:	ImmunoHorizons [Immunohorizons] 2020 Oct 09; Vol. 4 (10), pp. 608-626. Date of Electronic Publication: 2020 Oct 09.
DOI:	10.4049/immunohorizons.2000060
Abstrakt:	The protective efficacy of a live-attenuated HSV type 1 (HSV-1) vaccine, HSV-1 0∆ nuclear location signal (NLS), was evaluated in mice prophylactically in response to ocular HSV-1 challenge. Mice vaccinated with the HSV-1 0∆NLS were found to be more resistant to subsequent ocular virus challenge in terms of viral shedding, spread, the inflammatory response, and ocular pathology in a dose-dependent fashion. Specifically, a strong neutralizing Ab profile associated with low virus titers recovered from the cornea and trigeminal ganglia was observed in vaccinated mice in a dose-dependent fashion with doses ranging from 1 × 10 3 to 1 × 10 5 PFU HSV-1 0∆NLS. This correlation also existed in terms of viral latency in the trigeminal ganglia, corneal neovascularization, and leukocyte infiltration and expression of inflammatory cytokines and chemokines in infected tissue with the higher doses (1 × 10 4 -1 × 10 5 PFU) of the HSV-1 0∆NLS-vaccinated mice, displaying reduced viral latency, ocular pathology, or inflammation in comparison with the lowest dose (1 × 10 3 PFU) or vehicle vaccine employed. Fifteen HSV-1-encoded proteins were uniquely recognized by antisera from high-dose (1 × 10 5 PFU)-vaccinated mice in comparison with low-dose (1 × 10 3 PFU)- or vehicle-vaccinated animals. Passive immunization using high-dose-vaccinated, but not low-dose-vaccinated, mouse sera showed significant efficacy against ocular pathology in HSV-1-challenged animals. In summary, we have identified the minimal protective dose of HSV-1 0∆NLS vaccine in mice to prevent HSV-mediated disease and identified candidate proteins that may be useful in the development of a noninfectious prophylactic vaccine against the insidious HSV-1 pathogen. (Copyright © 2020 The Authors.)
Databáze:	MEDLINE
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