Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model.
Comparison of the efficacy of a commercial inactivated influenza A/H1N1/pdm09 virus (pH1N1) vaccine and two experimental M2e-based vaccines against pH1N1 challenge in the growing pig model.
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DOI：
10.1371/journal.pone.0191739
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Tan M
中科院分区：
文献类型：
--
作者：
Opriessnig T;Gauger PC;Gerber PF;Castro AMMG;Shen H;Murphy L;Digard P;Halbur PG;Xia M;Jiang X;Tan M
在北美猪中发现的甲型猪流感病毒 (IAV-S) 多种多样，异源毒株之间缺乏交叉保护是一个令人担忧的问题。本研究的目的是在生长猪模型中使用 IAV M2 胞外域 (M2e) 表位作为抗原，比较商业灭活 A/H1N1/pdm09 (pH1N1) 疫苗和两种新型亚单位疫苗。 39 头 2 周龄 IAV 阴性猪被随机分配到 5 个组和房间。在 3 周龄和 5 周龄时，猪分别鼻内接种实验性亚单位颗粒疫苗 (NvParticle/M2e) 或基于亚单位复合物的疫苗 (NvComplex/M2e)，或肌肉注射商业灭活疫苗 (Inact/pH1N1)。在 7 周龄时，用 pH1N1 病毒攻击猪或进行假接种。 pH1N1 攻击后 5 天进行尸检 (dpc)。在攻击时，其中一只 Inact/pH1N1 猪已根据 IAV 核蛋白 ELISA 进行血清转化，与所有其他组相比，Inact/pH1N1 猪具有显着更高的 pdm09H1N1 血凝抑制 (HI) 滴度，并且在 NvParticle/M2e 和 NvComplex/M2e 猪中检测到 M2e 特异性 IgG 反应，且组平均值显着较高。 NvComplex/M2e 组与 SHAMVAC-NEG 猪相比。攻击后，与所有其他 pH1N1 感染组相比，Inact/pH1N1 猪的鼻腔 IAV RNA 脱落显着减少，并且该组口腔液中的 IAV RNA 也减少。肉眼可见的肺部病变的特征是轻度至重度、多灶性至弥漫性、颅腹侧深紫色实变区域，这是IAV感染的典型特征，并且与NvParticle/M2e、NvComplex/M2e和SHAMVAC-IAV猪相似。 SHAMVAC-NEG 和 Inact/pH1N1 猪的病变明显较轻。在本研究的条件下，商业 Inact/pH1N1 特异性疫苗有效地保护猪免受同源攻击，临床症状减少、鼻腔分泌物和口腔液中病毒脱落以及宏观和微观损伤减少，而使用基于 M2e 表位的实验性亚单位疫苗进行鼻内接种则没有效果。结果进一步强调了在猪身上使用 IAV-S 型特异性疫苗的重要性。
Swine influenza A viruses (IAV-S) found in North American pigs are diverse and the lack of cross-protection among heterologous strains is a concern. The objective of this study was to compare a commercial inactivated A/H1N1/pdm09 (pH1N1) vaccine and two novel subunit vaccines, using IAV M2 ectodomain (M2e) epitopes as antigens, in a growing pig model. Thirty-nine 2-week-old IAV negative pigs were randomly assigned to five groups and rooms. At 3 weeks of age and again at 5 weeks of age, pigs were vaccinated intranasally with an experimental subunit particle vaccine (NvParticle/M2e) or a subunit complex-based vaccine (NvComplex/M2e) or intramuscularly with a commercial inactivated vaccine (Inact/pH1N1). At 7 weeks of age, the pigs were challenged with pH1N1 virus or sham-inoculated. Necropsy was conducted 5 days post pH1N1 challenge (dpc). At the time of challenge one of the Inact/pH1N1 pigs had seroconverted based on IAV nucleoprotein-based ELISA, Inact/pH1N1 pigs had significantly higher pdm09H1N1 hemagglutination inhibition (HI) titers compared to all other groups, and M2e-specific IgG responses were detected in the NvParticle/M2e and the NvComplex/M2e pigs with significantly higher group means in the NvComplex/M2e group compared to SHAMVAC-NEG pigs. After challenge, nasal IAV RNA shedding was significantly reduced in Inact/pH1N1 pigs compared to all other pH1N1 infected groups and this group also had reduced IAV RNA in oral fluids. The macroscopic lung lesions were characterized by mild-to-severe, multifocal-to-diffuse, cranioventral dark purple consolidated areas typical of IAV infection and were similar for NvParticle/M2e, NvComplex/M2e and SHAMVAC-IAV pigs. Lesions were significantly less severe in the SHAMVAC-NEG and the Inact/pH1N1pigs. Under the conditions of this study, a commercial Inact/pH1N1 specific vaccine effectively protected pigs against homologous challenge as evidenced by reduced clinical signs, virus shedding in nasal secretions and oral fluids and reduced macroscopic and microscopic lesions whereas intranasal vaccination with experimental M2e epitope-based subunit vaccines did not. The results further highlight the importance using IAV-S type specific vaccines in pigs.
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82.9
作者：
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