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马流感(H3N8)病毒灭活疫苗在小鼠模型中的免疫原性和保护效力。

Immunogenicity and protective efficacy of inactivated equine influenza (H3N8) virus vaccine in murine model.

机构信息

ICAR-National Research Centre on Equines, Hisar, Haryana, 125001, India; Indian Veterinary Research Institute, Bareilly, UP, 243122, India.

ICAR-National Research Centre on Equines, Hisar, Haryana, 125001, India.

出版信息

Vet Microbiol. 2017 Oct;210:188-196. doi: 10.1016/j.vetmic.2017.08.013. Epub 2017 Aug 26.

Abstract

Equine influenza viruses (EIVs) are responsible for acute contagious respiratory infection in equines and the disease remains a major threat for equine population throughout the world despite vaccination strategies in place. The present study was aimed to assess the suitability of BALB/c mice as a potential small animal model for preliminary screening of EI vaccine candidates. For this, we evaluated the immunogenicity and protective efficacy of an inactivated EIV (H3N8) vaccine in BALB/c mouse model after challenge with homologous H3N8 virus (Clade 2 virus, Florida sublineage) through serology, clinical signs, gross and histopathology lesions with grading, immunohistochemistry and virus quantification. Serological responses in immunized mice were evaluated by haemagglutination inhibition assay (HAI) and antibodies were subtyped by ELISA. The vaccine induced optimum protective antibody titre on 49 dpi along with balanced Th1/Th2 responses. Immunized mice were well protected against EIV challenge as evident by significant rise in serum antibody titre which concurred with mild clinical signs, early recovery, lower gross and histopathological lesions score, less severe intensity of viral antigen distribution, restricted virus replication in respiratory tract and less virus detection in nasal washes for short duration. The duration of the viral load was also lower and only for brief period as compared to unvaccinated challenged mice. In conclusion, induction of H3N8 specific antibody response and protection against H3N8 challenge proves that egg grown inactivated H3N8 whole virus vaccine would provide an effective intercession against H3N8 virus. In addition, BALB/c mouse can serve as an attractive tool for adjudging protective efficacy of vaccine candidates prior to final testing in equines.

摘要

马流感病毒(EIVs)可引起马属动物的急性传染性呼吸道感染,尽管已采取疫苗接种策略,但该疾病仍然是全球马属动物的主要威胁。本研究旨在评估 BALB/c 小鼠作为初步筛选 EI 疫苗候选物的潜在小动物模型的适用性。为此,我们通过血清学、临床症状、大体和组织病理学病变评分、免疫组织化学和病毒定量,评估了灭活 EIV(H3N8)疫苗在同源 H3N8 病毒(Clade 2 病毒,佛罗里达亚系)攻毒后 BALB/c 小鼠模型中的免疫原性和保护效力。通过血凝抑制试验(HAI)评估免疫小鼠的血清学反应,并通过 ELISA 对抗体进行分型。疫苗在 49dpi 时诱导最佳的保护抗体滴度,同时平衡 Th1/Th2 反应。免疫小鼠受到 EIV 攻毒的良好保护,这表现为血清抗体滴度显著升高,同时临床症状轻微、早期恢复、大体和组织病理学病变评分较低、病毒抗原分布的严重程度较轻、呼吸道病毒复制受限以及鼻腔冲洗中病毒检测时间短。与未接种攻毒的小鼠相比,病毒载量的持续时间也更短,仅为短暂时间。总之,诱导 H3N8 特异性抗体反应并对 H3N8 攻毒产生保护作用证明,在鸡蛋中生长的灭活 H3N8 全病毒疫苗可提供针对 H3N8 病毒的有效干预。此外,BALB/c 小鼠可作为评估候选疫苗保护效力的有吸引力的工具,然后再在马中进行最终测试。

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