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评估用选定佐剂配制的重组猪肺炎支原体P97/P102旁系同源物作为猪支原体肺炎疫苗的效果。

Evaluation of recombinant Mycoplasma hyopneumoniae P97/P102 paralogs formulated with selected adjuvants as vaccines against mycoplasmal pneumonia in pigs.

作者信息

Woolley Lauren K, Fell Shayne A, Gonsalves Jocelyn R, Raymond Benjamin B A, Collins Damian, Kuit Tracey A, Walker Mark J, Djordjevic Steven P, Eamens Graeme J, Jenkins Cheryl

机构信息

NSW Department of Primary Industries, Elizabeth Macarthur Agricultural Institute, Menangle, NSW 2568, Australia; School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522, Australia.

NSW Department of Primary Industries, Elizabeth Macarthur Agricultural Institute, Menangle, NSW 2568, Australia.

出版信息

Vaccine. 2014 Jul 23;32(34):4333-41. doi: 10.1016/j.vaccine.2014.06.008. Epub 2014 Jun 12.

DOI:10.1016/j.vaccine.2014.06.008
PMID:24930717
Abstract

Pig responses to recombinant subunit vaccines containing fragments of eight multifunctional adhesins of the Mycoplasma hyopneumoniae (Mhp) P97/P102 paralog family formulated with Alhydrogel(®) or Montanide™ Gel01 were compared with a commercial bacterin following experimental challenge. Pigs, vaccinated intramuscularly at 9, 12 and 15 weeks of age with either of the recombinant formulations (n=10 per group) or Suvaxyn(®) M. hyo (n=12), were challenged with Mhp strain Hillcrest at 17 weeks of age. Unvaccinated, challenged pigs (n=12) served as a control group. Coughing was assessed daily. Antigen-specific antibody responses were monitored by ELISA in serum and tracheobronchial lavage fluid (TBLF), while TBLF was also assayed for cytokine responses (ELISA) and bacterial load (qPCR). At slaughter, gross and histopathology of lungs were quantified and damage to epithelial cilia in the porcine trachea was evaluated by scanning electron microscopy. Suvaxyn(®) M. hyo administration induced significant serological responses against Mhp strain 232 whole cell lysates (wcl) and recombinant antigen F3P216, but not against the remaining vaccine subunit antigens. Alhydrogel(®) and Montanide™ Gel01-adjuvanted antigen induced significant antigen-specific IgG responses, with the latter adjuvant eliciting comparable Mhp strain 232 wcl specific IgG responses to Suvaxyn(®) M. hyo. No significant post-vaccination antigen-specific mucosal responses were detected with the recombinant vaccinates. Suvaxyn(®) M. hyo was superior in reducing clinical signs, lung lesion severity and bacterial load but the recombinant formulations offered comparable protection against cilial damage. Lower IL-1β, TNF-α and IL-6 responses after challenge were associated with reduced lung lesion severity in Suvaxyn(®) M. hyo vaccinates, while elevated pathology scores in recombinant vaccinates corresponded to cytokine levels that were similarly elevated as in unvaccinated pigs. This study highlights the need for continued research into protective antigens and vaccination strategies that will prevent Mhp colonisation and establishment of infection.

摘要

将含有猪肺炎支原体(Mhp)P97/P102旁系同源家族的八种多功能黏附素片段的重组亚单位疫苗与佐剂氢氧化铝(Alhydrogel®)或Montanide™ Gel01混合,对猪进行免疫,在实验性攻毒后,将其反应与一种商业菌苗进行比较。在9、12和15周龄时,给猪肌肉注射两种重组疫苗制剂之一(每组n = 10)或Suvaxyn®猪肺炎支原体疫苗(n = 12),在17周龄时用Mhp Hillcrest菌株进行攻毒。未接种疫苗、攻毒的猪(n = 12)作为对照组。每天评估咳嗽情况。通过ELISA检测血清和气管支气管灌洗液(TBLF)中的抗原特异性抗体反应,同时对TBLF进行细胞因子反应检测(ELISA)和细菌载量检测(qPCR)。屠宰时,对肺的大体和组织病理学进行量化,并通过扫描电子显微镜评估猪气管上皮纤毛的损伤情况。接种Suvaxyn®猪肺炎支原体疫苗可诱导针对Mhp菌株232全细胞裂解物(wcl)和重组抗原F3P216的显著血清学反应,但对其余疫苗亚单位抗原无反应。氢氧化铝(Alhydrogel®)和Montanide™ Gel01佐剂的抗原诱导了显著的抗原特异性IgG反应,后者佐剂诱导的针对Mhp菌株232 wcl的特异性IgG反应与Suvaxyn®猪肺炎支原体疫苗相当。重组疫苗接种后未检测到显著的抗原特异性黏膜反应。Suvaxyn®猪肺炎支原体疫苗在减轻临床症状、肺损伤严重程度和细菌载量方面更优,但重组疫苗制剂在防止纤毛损伤方面提供了相当的保护。攻毒后较低的IL-1β、TNF-α和IL-6反应与接种Suvaxyn®猪肺炎支原体疫苗的猪肺损伤严重程度降低有关,而重组疫苗接种猪的病理学评分升高与细胞因子水平升高相对应,与未接种疫苗的猪相似。本研究强调需要继续研究保护性抗原和疫苗接种策略,以预防Mhp定植和感染的建立。

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