超级细菌疫苗研究的挑战与策略

邹全明; 曾浩

doi:10.16016/j.1000-5404.201909029

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超级细菌疫苗研究的挑战与策略

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- 超级细菌疫苗研究的挑战与策略
- Development of vaccines against superbugs: challenges and strategies
- 第三军医大学学报 2019年41卷第19期页码：1823-1826
- 作者机构：
  
  400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系微生物与生化药学教研室，国家免疫生物制品工程技术研究中心
- 作者简介：
  
  [邹全明，博士，教授，博士生导师。担任国务院学位委员会学科评议组药学组成员、第十届国家药典委员会委员。主持“十二五”国家科技支撑计划、国家高技术研究发展计划(863计划)、国家科技重大专项等国家及军队重大、重点课题12项。成功研制世界首个预防胃病的幽门螺杆菌疫苗并获1类新药证书，获国家技术发明二等奖。主持研究的国际首个五组分金黄色葡萄球菌疫苗已开展Ⅱ期临床试验。以第一发明人获国家发明专利授权25项，国际PCT专利4项。目前正在主持研制的原创疫苗5个。以通信作者发表并被SCI收录的论文80余篇，其中，在《柳叶刀》(Lancet)发表论著1篇。主要从事临床微生物、临床免疫、分子免疫学、生物制药方面的研究。E-mail:qmzou2007@163.comZOU Quanming, E-mail:qmzou2007@163.com
- 基金信息：
  
  军队后勤科研重大项目(AWS16J029);军特药保密专项课题(2016ZX09J16102-002);国家自然科学基金面上项目(81571621)
- DOI：10.16016/j.1000-5404.201909029
  中图分类号： R378;R979.5
- 收稿：2019-09-05，
  
  修回：2019-09-09，
  
  纸质出版：2019-10-15
- 稿件说明：
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邹全明, 曾浩. 超级细菌疫苗研究的挑战与策略[J]. 第三军医大学学报, 2019,41(19):1823-1826.

Quanming ZOU, Hao ZENG. Development of vaccines against superbugs: challenges and strategies[J]. Journal of Third Military Medical University, 2019, 41(19): 1823-1826.
邹全明, 曾浩. 超级细菌疫苗研究的挑战与策略[J]. 第三军医大学学报, 2019,41(19):1823-1826. DOI： 10.16016/j.1000-5404.201909029.

Quanming ZOU, Hao ZENG. Development of vaccines against superbugs: challenges and strategies[J]. Journal of Third Military Medical University, 2019, 41(19): 1823-1826. DOI： 10.16016/j.1000-5404.201909029.

摘要

超级细菌(superbugs)泛指那些对多种抗生素具有耐药性的细菌，专业术语是“多重耐药性细菌”。2017年，WHO列出严重威胁人类的12种耐药细菌清单，金黄色葡萄球菌、鲍曼不动杆菌、铜绿假单胞菌和肺炎克雷伯菌在清单中分别位列G

菌首位和G

菌前3位。因现在大部分的抗生素对它们已失去效力，全人类将面临难以承受的巨大挑战与威胁。疫苗是防控致病菌流行感染最佳的科学手段。我国科学家团队已研制国际首个靶标最多、效果最佳的金黄色葡萄球菌疫苗，正开展Ⅱ期临床试验。近20年来，欧美国家先后研发20余种超级细菌疫苗进行临床试验，但尚无一项成功。超级细菌疫苗研究面临巨大的挑战，如超级细菌致病机制不详，超级细菌疫苗如何在易感人群快速起效，超级细菌动物模型、临床流行病学基础数据和临床试验评价的关键技术及标准缺乏等均是目前超级细菌研究亟待解决的难题。我们建议今后的研究围绕以下几个方面进行:①建立保护性抗原表位大数据及高通量筛选新技术；②研究耐药菌疫苗快速起效机制及新技术；③开展超级细菌疫苗使用人群的免疫应答规律及特征研究；④建立成熟、稳定的超级细菌感染动物模型；⑤运用大数据、人工智能、基因组学等建立超级细菌流行病学大数据库和菌种资源库；⑥开展细菌疫苗的免疫保护机制及其核心指标的研究。

Abstract

Superbugs are broadly referred to the bacteria that are resistant to multiple antibiotics

and the special term is "multi-drug resistant bacteria". In 2017

WHO listed 12 antibiotic-resistant bacteria that can cause severe illness or death in humans as the global priority pathogens

including methicillin-resistant

Staphylococcus aureus

(MRSA)

Acinetobacter baumannii

Pseudomonas aeruginosa

and

Klebsiella pneumonia

. MRSA ranks the first among Gram-positive bacteria and the others take the top 3 among Gram-negative bacteria. Because most of antibiotics have lost their effectiveness to them

human beings have to face enormous challenges and threats that cannot be tolerated. Vaccine is one of the most effective preventive measures. Scientists from China have developed a unique effective vaccine against MRSA with the most multivalent and antigenic components in the world

which has been entered the phase Ⅱ clinical trial. In the past 2 decades

about 20 vaccines against superbugs were developed in the European and American countries

but none has demonstrated protection in human trials. The development of vaccine against superbugs is still an enormous challeng

e to scientist. There are some problems that need to be solved in the current studies concerning superbugs

such as their pathogenesis

how the vaccines work rapidly in susceptible populations

animal model for superbugs

basic data in clinical epidemiology and assessment for clinical trials

and other key techniques and standards. We suggest that future researches should be carried out in the following aspects: ① establishment of big data about protective antigen epitopes and high-throughput screening techniques; ② rapid onset mechanism and new technology of superbug vaccine; ③ rule and characteristics of immune responses of superbug vaccine; ④ establishment of a mature and stable animal model of superbug infection; ⑤ establishment of a database of superbug epidemiology and strains base on big data

artificial intelligence and genomics; ⑥ immune protection mechanisms and core indicators of superbug vaccines.

关键词

Keywords

references

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