在生长猪模型中,比较一种市售甲型H1N1/pdm09流感病毒(pH1N1)灭活疫苗和两种基于M2e的实验性疫苗对pH1N1攻击的效力。

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.

作者信息

Opriessnig Tanja, Gauger Phillip C, Gerber Priscilla F, Castro Alessandra M M G, Shen Huigang, Murphy Lita, Digard Paul, Halbur Patrick G, Xia Ming, Jiang Xi, Tan Ming

机构信息

The Roslin Institute and The Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.

Department of Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, Iowa, United States of America.

出版信息

PLoS One. 2018 Jan 30;13(1):e0191739. doi: 10.1371/journal.pone.0191739. eCollection 2018.

Abstract

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.

摘要

在北美猪群中发现的甲型流感病毒(IAV-S)具有多样性,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比较一种商业化的灭活A/H1N1/pdm09(pH1N1)疫苗和两种新型亚单位疫苗,这两种新型亚单位疫苗使用IAV M2胞外域(M2e)表位作为抗原。39头2周龄的IAV阴性猪被随机分配到5个组和5个栏舍。在3周龄和5周龄时,猪分别经鼻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),或经肌肉接种商业化灭活疫苗(Inact/pH1N1)。在7周龄时,猪用pH1N1病毒进行攻毒或假接种。在pH1N1攻毒后5天(dpc)进行剖检。在攻毒时,基于IAV核蛋白的ELISA检测显示,Inact/pH1N1组中有一头猪发生了血清转化,与所有其他组相比,Inact/pH1N1组猪的pdm09H1N1血凝抑制(HI)效价显著更高,并且在NvParticle/M2e组和NvComplex/M2e组猪中检测到了M2e特异性IgG反应,与SHAMVAC-NEG组相比,NvComplex/M2e组的组均值显著更高。攻毒后,与所有其他pH1N1感染组相比,Inact/pH1N1组猪的鼻腔IAV RNA脱落显著减少,并且该组猪的口腔液中IAV RNA也减少。宏观肺损伤的特征为轻度至重度、多灶性至弥漫性、颅腹侧暗紫色实变区域,这是IAV感染的典型表现,NvParticle/M2e组、NvComplex/M2e组和SHAMVAC-IAV组猪的情况相似。SHAMVAC-NEG组和Inact/pH1N1组猪的损伤严重程度显著较低。在本研究条件下,一种商业化的Inact/pH1N1特异性疫苗有效地保护猪免受同源攻毒,表现为临床症状减轻、鼻分泌物和口腔液中的病毒脱落减少以及宏观和微观损伤减轻,而经鼻接种基于实验性M2e表位的亚单位疫苗则没有这种效果。结果进一步凸显了在猪中使用IAV-S型特异性疫苗的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c50/5790244/f04508123062/pone.0191739.g001.jpg

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