MERS-CoV疫苗研究取得重要进展

Jianbo · 发表于 2015-11-5 15:51:29

中东呼吸综合征冠状病毒（MERS-CoV）最早于2012年从中东地区一名急性呼吸道感染并发急性肾衰竭的患者体内分离，目前已扩散到世界20多个国家和地区。据WHO报道，截止到2015年10月12日，全球共报道实验室确诊病例1595人，其中死亡571人，病死率达35.8%。其中2015年5-7月间韩国因一例MERS-CoV输入导致186人感染、35人病死的暴发事件，直接和间接经济损失达100亿美元。其中有1个MERS感染病例从韩国输入我国广东。目前，国内外尚无有效特异性药物，临床主要以对症支持治疗为主。传统的全病毒灭活疫苗研发策略存在生物安全隐患并产生疫苗接种后再感染可能导致免疫病理等现象等，为有效防控MERS-CoV感染暴发与流行，提高我国应对MERS-CoV等突发烈性传染病的应急技术贮备能力，急需对抗MERS-CoV感染的免疫保护性抗原与适用性免疫保护策略进行研究确定，并研发有效基因工程疫苗。

中国疾控中心病毒病所在国家十二五传染病重大专项课题资助下，开展了多种技术策略的MERS-CoV基因工程疫苗研制，其中关于多肽苗、RBD亚单位与重组腺病毒MERS疫苗的多项研究结果相继发表于Viral Immunology、Plos One与Immunology杂志，并在国际会议进行交流。基于前期在小鼠中MERS-CoV RBD亚单位疫苗免疫结果及MERS-CoV恒河猴模型研究进展，病毒病所科研人员通过与中国医学科学院实验动物所、中国科学院微生物研究所通力合作，首次在12只成年恒河猴模型中对MERS-CoV RBD亚单位疫苗的免疫应答特点及免疫保护效应进行了详尽研究。结果发现：不同剂量RBD亚单位疫苗与铝佐剂通过肌肉注射恒河猴后，可以诱发明显的体液免疫（抗体与中和抗体）与细胞免疫应答，且加强免疫后中和抗体可维持数周；在高剂量MERS-CoV病毒气管攻毒后，与对照组恒河猴相比，RBD蛋白疫苗免疫组显示出明显免疫保护效果，如： X线胸片的肺部阴影出现时间推迟，阴影面积缩小；病理检查发现，免疫的恒河猴肺部和气管炎性改变减轻；呼吸道样品核酸检测与病毒分离结果也表现为疫苗免疫组明显低于对照组。这是国际上首次在非人灵长类动物模型上对MERS-CoV亚单位疫苗进行免疫保护效果评价。该研究成果总结为研究论文“Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge”，最近发表于《EbioMedicine》。文章第一作者为中国疾控中心2013级博士生蓝佳明同学；文章通讯作者为中国疾控中心病毒病所应急技术中心谭文杰研究员与中国医学科学院实验动物所秦川教授。

《EbioMedicine》杂志为《Cell》和《Lancet》旗下的新出版转化医学国际期刊。该杂志邀请北卡罗纳大学Vineet D. Menachery博士专为该文撰写评述“MERS Vaccine Candidate Offers Promise, but Questions Remain”。认为蓝佳明等人发表的研究结果为基于RBD的冠状病毒疫苗研发与MERS-CoV感染防治提供了重要思路与技术指导。

本文来源：中国CDC病毒病预防控制所作者：谭文杰

原文链接 http://ivdc.chinacdc.cn/kyjz/201511/t20151105_121710.htm

rentianyixu · 发表于 2015-11-5 20:13:27

Research Article

Recombinant Receptor Binding Domain Protein Induces Partial Protective Immunity in Rhesus Macaques Against Middle East Respiratory Syndrome Coronavirus Challenge ☆

Received 24 June 2015, Revised 16 August 2015, Accepted 17 August 2015, Available online 18 August 2015
Highlights
•

In this study, we evaluated a recombinant receptor binding domain(rRBD) based subunit vaccine in a rhesus macaque model.

•

Significant and sustained immunuity in a rhesus macaque model were elicited by the rRBD vaccination.

•

Partial protection was observed in the vaccinated monkeys against the MERS-CoV challenge.

•

We suggest the partial protection in monkey against the MERS-CoV challenge may be conferred by neutralizing antibodies induced by rRBD immunity.

•

The study provided useful information for the development of a human vaccine against MERS-CoV infection.

AbstractBackground

Development an effective vaccine against Middle East respiratory syndrome coronavirus (MERS-CoV) is urgent and limited information is available on vaccination in nonhuman primate (NHP) model. We herein report of evaluating a recombinant receptor-binding domain (rRBD) protein vaccine in a rhesus macaque model.

Methods

Nine monkeys were randomly assigned to high-dose, low-dose and mock groups,which were immunized with different doses of rRBD plus alum adjuvant or adjuvant alone at different time points (0, 8, 25 weeks). Immunological analysis was conducted after each immunisation. Monkeys were challenged with MERS-CoV at 14 days after the final immunisation followed by observation for clinical signs and chest X-rays. Nasal, oropharyngeal and rectal swabs were also collected for analyses. Monkeys were euthanized 3 days after challenge and multiple specimens from tissues were collected for pathological, virological and immunological tests.

Conclusion

Robust and sustained immunological responses (including neutralisation antibody) were elicited by the rRBD vaccination. Besides, rRBD vaccination alleviated pneumonia with evidence of reduced tissue impairment and clinical manifestation in monkeys. Furthermore, the rRBD vaccine decreased viral load of lung, trachea and oropharyngeal swabs of monkeys. These data in NHP paves a way for further development of an effective human vaccine against MERS-CoV infection.

rojjer · 发表于 2015-11-5 22:47:59

厉害啊。为MERS疫苗研发提供支持！

		自动登录	找回密码
密码			立即注册