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减毒Lv17/WB/Rie1非洲猪瘟病毒(ASFV)中EP402R和EP153R的双缺失增强了安全性,提供了鉴别诊断兼容性,并赋予对II型强毒株的完全保护。

Double Deletion of EP402R and EP153R in the Attenuated Lv17/WB/Rie1 African Swine Fever Virus (ASFV) Enhances Safety, Provides DIVA Compatibility, and Confers Complete Protection Against a Genotype II Virulent Strain.

作者信息

Gallardo Carmina, Mészáros István, Soler Alejandro, Fernandez-Pinero Jovita, van den Born Erwin, Simón Alicia, Casado Nadia, Nieto Raquel, Perez Covadonga, Aldea Irene, Lopez-Chavarrias Vicente, Göltl Eszter, Olasz Ferenc, Magyar Tibor, Zádori Zoltán, Sánchez-Vizcaíno José Manuel, Arias Marisa

机构信息

European Union Reference Laboratory for African Swine Fever (EURL), Centro de Investigación en Sanidad Animal (CISA), Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Consejo Superior de Investigaciones Científicas (CSIC), Valdeolmos, 28130 Madrid, Spain.

HUN-REN Veterinary Medical Research Institute, Hungária krt. 21, 1143 Budapest, Hungary.

出版信息

Vaccines (Basel). 2024 Dec 13;12(12):1406. doi: 10.3390/vaccines12121406.

Abstract

African swine fever virus (ASFV) is a devastating disease affecting domestic and wild suids and causing significant economic losses in the global pig industry. Attenuated modified live virus (MLV) vaccines are the most promising approaches for vaccine development. This study aimed to evaluate the safety and efficacy of four recombinant ASFV genotype II strains, derived from the non-hemadsorbing (non-HAD) attenuated isolate Lv17/WB/Rie1, through the single or simultaneous deletion of virulence-associated genes. Recombinant viruses were engineered by deleting the , , and genes, either individually or in combination. Four recombinant strains were evaluated for safety and efficacy in domestic pigs vaccinated intramuscularly with 10 TCID₅₀. Clinical signs, viremia, virus shedding, and antibody responses were monitored. Protection efficacy was assessed by challenging vaccinated pigs with the virulent genotype II Armenia07 strain. Additionally, a reversion-to-virulence study involving an overdose of the vaccine candidate was conducted to evaluate its stability through serial immunizations. Deletion of the gene alone increased virulence, whereas the double deletion of and (Lv17/WB/Rie1-ΔCD) significantly enhanced safety while maintaining full protective efficacy. Vaccinated pigs exhibited reduced viremia, no virus shedding, and robust virus-specific antibody responses, achieving complete protection against Armenia07. The reversion-to-virulence study revealed potential but limited pathogenicity after multiple passages, indicating areas for improvement in vaccine stability. The Lv17/WB/Rie1-ΔCD strain demonstrates excellent safety and efficacy, along with potential DIVA (differentiating infected from vaccinated animals) compatibility, positioning it as a strong candidate for an ASFV MLV vaccine. Further research is needed to refine the vaccine and address the potential risks of reversion to virulence.

摘要

非洲猪瘟病毒(ASFV)是一种毁灭性疾病,影响家猪和野猪,并给全球养猪业造成重大经济损失。减毒活疫苗(MLV)是疫苗开发中最具前景的方法。本研究旨在评估四种源自非血细胞吸附(non-HAD)减毒株Lv17/WB/Rie1的重组ASFV基因型II菌株,通过单独或同时缺失与毒力相关基因后的安全性和有效性。通过单独或组合缺失、和基因来构建重组病毒。对四种重组菌株进行安全性和有效性评估,给家猪肌肉注射10 TCID₅₀进行接种。监测临床症状、病毒血症、病毒排泄及抗体反应。通过用强毒基因型II亚美尼亚07株攻击接种疫苗的猪来评估保护效力。此外,进行了一项涉及过量候选疫苗的毒力返强研究,通过连续免疫来评估其稳定性。单独缺失基因会增加毒力,而同时缺失和(Lv17/WB/Rie1-ΔCD)可显著提高安全性,同时保持完全的保护效力。接种疫苗的猪病毒血症减轻,无病毒排泄,且产生强烈的病毒特异性抗体反应,对亚美尼亚07株实现了完全保护。毒力返强研究显示多次传代后有潜在但有限的致病性,表明疫苗稳定性方面有待改进的领域。Lv17/WB/Rie1-ΔCD菌株显示出优异的安全性和有效性,以及潜在的鉴别诊断能力(区分感染动物和接种疫苗动物),使其成为ASFV MLV疫苗的有力候选者。需要进一步研究来优化疫苗并解决毒力返强的潜在风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/04f1/11680264/200fa25ef87a/vaccines-12-01406-g001.jpg

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