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

ABSTRACT: 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 × 103 to 1 × 105 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 × 104-1 × 105 PFU) of the HSV-1 0?NLS-vaccinated mice, displaying reduced viral latency, ocular pathology, or inflammation in comparison with the lowest dose (1 × 103 PFU) or vehicle vaccine employed. Fifteen HSV-1-encoded proteins were uniquely recognized by antisera from high-dose (1 × 105 PFU)-vaccinated mice in comparison with low-dose (1 × 103 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.

SUBMITTER: Carr DJJ

PROVIDER: S-EPMC7668388 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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

Carr Daniel J J DJJ Gmyrek Grzegorz B GB Filiberti Adrian A Berube Amanda N AN Browne William P WP Gudgel Brett M BM Sjoelund Virginie H VH

ImmunoHorizons 20201009 10

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 ...[more]

PMID: 33037098

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Project description:We analyzed several features of five currently available delta-proteobacterial genomes, including two aerobic bacteria exhibiting predatory behavior and three anaerobic sulfate-reducing bacteria. The delta genomes are distinguished from other bacteria by several properties: (i) The delta genomes contain two "giant" S1 ribosomal protein genes in contrast to all other bacterial types, which encode a single or no S1; (ii) in most delta-proteobacterial genomes the major ribosomal protein (RP) gene cluster is near the replication terminus whereas most bacterial genomes place the major RP cluster near the origin of replication; (iii) the delta genomes possess the rare combination of discriminating asparaginyl and glutaminyl tRNA synthetase (AARS) together with the amido-transferase complex (Gat CAB) genes that modify Asp-tRNA(Asn) into Asn-tRNA(Asn) and Glu-tRNA(Gln) into Gln-tRNA(Gln); (iv) the TonB receptors and ferric siderophore receptors that facilitate uptake and removal of complex metals are common among delta genomes; (v) the anaerobic delta genomes encode multiple copies of the anaerobic detoxification protein rubrerythrin that can neutralize hydrogen peroxide; and (vi) sigma(54) activators play a more important role in the delta genomes than in other bacteria. delta genomes have a plethora of enhancer binding proteins that respond to environmental and intracellular cues, often as part of two-component systems; (vii) delta genomes encode multiple copies of metallo-beta-lactamase enzymes; (viii) a host of secretion proteins emphasizing SecA, SecB, and SecY may be especially useful in the predatory activities of Myxococcus xanthus; (ix) delta proteobacteria drive many multiprotein machines in their periplasms and outer membrane, including chaperone-feeding machines, jets for slime secretion, and type IV pili. Bdellovibrio replicates in the periplasm of prey cells. The sulfate-reducing delta proteobacteria metabolize hydrogen and generate a proton gradient by electron transport. The predicted highly expressed genes from delta genomes reflect their different ecologies, metabolic strategies, and adaptations.

Dataset Information

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

Publications

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

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