A novel neuro-attenuated vaccine candidate with excellent safety and protective efficacy against highly virulent Feline Herpesvirus-1

IF 2.4 2区 农林科学 Q3 MICROBIOLOGY Veterinary microbiology Pub Date : 2024-10-15 DOI:10.1016/j.vetmic.2024.110276
Mingyu Qi , Mengfang Yang , Ruxue Luo , Lingying Fang , Yixi Chen , Jianuo Gao , Zhe Jiao , Yuejun Shi , Guiqing Peng
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Abstract

Feline herpesvirus 1 (FHV-1) is a major pathogen responsible for respiratory, ocular and nervous system symptoms in felines. FHV-1 can remain latenct in ganglia and is difficult to eliminate completely with drug treatment. Currently, commercially FHV-1 vaccines are not sufficiently effective and provide only limited durations of protection. To enhance vaccine efficacy and reduce latent virus in tissues, two gene deletion mutants of FHV-1 conveyed excellent proliferation ability, genetic stability and attenuated FHV-1 virulence were constructed by CRISPR/Cas9-mediated homologous recombination, designated as FHV-△US3 and FHV-△UL50. Recombinant FHV-1 induce stronger cellular and humoral immune responses, as well as better protective effects than those of commercial vaccines. Notably, FHV-△US3 and FHV-△UL50 reveal neuro-attenuated, as viral residue in the trigeminal ganglia are significantly reduced. The knockout of the UL50 gene in FHV-1 has not been previously reported. In this study, we aimed to evaluate the safety and immunogenicity of FHV-△UL50, highlighting its potential as a novel neuroattenuated vaccine candidate.
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一种新型神经减毒候选疫苗,对高致病性猫疱疹病毒-1 具有极佳的安全性和保护效力。
猫疱疹病毒 1 (FHV-1) 是导致猫科动物出现呼吸道、眼部和神经系统症状的主要病原体。FHV-1 可潜伏在神经节中,很难通过药物治疗彻底清除。目前,市售的 FHV-1 疫苗效果不佳,只能提供有限的保护期。为了提高疫苗疗效并减少组织中的潜伏病毒,我们通过 CRISPR/Cas9 介导的同源重组技术构建了两个基因缺失的 FHV-1 突变体,这两个突变体分别被命名为 FHV-△US3 和 FHV-△UL50,它们具有优异的增殖能力、遗传稳定性和减毒能力。与商业疫苗相比,重组 FHV-1 能诱导更强的细胞和体液免疫反应,以及更好的保护效果。值得注意的是,FHV-△US3 和 FHV-△UL50 揭示了神经减毒作用,三叉神经节中的病毒残留明显减少。之前还没有关于 FHV-1 中 UL50 基因敲除的报道。在这项研究中,我们旨在评估FHV-△UL50的安全性和免疫原性,突出其作为新型神经减毒疫苗候选物的潜力。
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来源期刊
Veterinary microbiology
Veterinary microbiology 农林科学-兽医学
CiteScore
5.90
自引率
6.10%
发文量
221
审稿时长
52 days
期刊介绍: Veterinary Microbiology is concerned with microbial (bacterial, fungal, viral) diseases of domesticated vertebrate animals (livestock, companion animals, fur-bearing animals, game, poultry, fish) that supply food, other useful products or companionship. In addition, Microbial diseases of wild animals living in captivity, or as members of the feral fauna will also be considered if the infections are of interest because of their interrelation with humans (zoonoses) and/or domestic animals. Studies of antimicrobial resistance are also included, provided that the results represent a substantial advance in knowledge. Authors are strongly encouraged to read - prior to submission - the Editorials (''Scope or cope'' and ''Scope or cope II'') published previously in the journal. The Editors reserve the right to suggest submission to another journal for those papers which they feel would be more appropriate for consideration by that journal. Original research papers of high quality and novelty on aspects of control, host response, molecular biology, pathogenesis, prevention, and treatment of microbial diseases of animals are published. Papers dealing primarily with immunology, epidemiology, molecular biology and antiviral or microbial agents will only be considered if they demonstrate a clear impact on a disease. Papers focusing solely on diagnostic techniques (such as another PCR protocol or ELISA) will not be published - focus should be on a microorganism and not on a particular technique. Papers only reporting microbial sequences, transcriptomics data, or proteomics data will not be considered unless the results represent a substantial advance in knowledge. Drug trial papers will be considered if they have general application or significance. Papers on the identification of microorganisms will also be considered, but detailed taxonomic studies do not fall within the scope of the journal. Case reports will not be published, unless they have general application or contain novel aspects. Papers of geographically limited interest, which repeat what had been established elsewhere will not be considered. The readership of the journal is global.
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