气候变化领域集成服务门户(CCPortal): Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice

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DOI	10.1073/pnas.2013730118
	Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice
	Hanna C.C.; Ashhurst A.S.; Quan D.; Maxwell J.W.C.; Britton W.J.; Payne R.J.
发表日期	2021
ISSN	00278424
卷号	118 期号:4
英文摘要	The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis. Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam2Cys-SK4 or Pam3Cys-SK4. These were produced by chemical synthesis using a peptide ligation strategy. The synthetic self-adjuvanting vaccines generated powerful local CD4+ T cell responses against ESAT6 and provided significant protection in the lungs from virulent M. tuberculosis aerosol challenge when administered to the pulmonary mucosa of mice. The flexible synthetic platform we describe, which allows incorporation of adjuvants to multiantigenic vaccines, represents a general approach that can be applied to rapidly assess vaccination strategies in preclinical models for a range of diseases, including against novel pandemic pathogens such as SARS-CoV-2. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Chemical protein synthesis; Mucosal vaccination; Peptide ligation; Self-adjuvanting; Tuberculosis
语种	英语
scopus关键词	bacterial antigen; bacterial protein; BCG vaccine; ESAT-6 protein, Mycobacterium tuberculosis; immunological adjuvant; recombinant vaccine; Tlr2 protein, mouse; toll like receptor 2; vaccine; animal; C57BL mouse; CD4+ T lymphocyte; disease model; female; immunology; mouse; Mycobacterium tuberculosis; prevention and control; tuberculosis; Adjuvants, Immunologic; Animals; Antigens, Bacterial; Bacterial Proteins; BCG Vaccine; CD4-Positive T-Lymphocytes; COVID-19; Disease Models, Animal; Female; Mice; Mice, Inbred C57BL; Mycobacterium tuberculosis; SARS-CoV-2; Toll-Like Receptor 2; Tuberculosis; Tuberculosis Vaccines; Vaccines, Conjugate; Vaccines, Synthetic
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180886
作者单位	School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia; Tuberculosis Research Program, Centenary Institute, University of Sydney, Camperdown, NSW 2006, Australia; Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2006, Australia; Department of Clinical Immunology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia; Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science, University of Sydney, Sydney, NSW 2006, Australia
推荐引用方式 GB/T 7714	Hanna C.C.,Ashhurst A.S.,Quan D.,et al. Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice[J],2021,118(4).
APA	Hanna C.C.,Ashhurst A.S.,Quan D.,Maxwell J.W.C.,Britton W.J.,&Payne R.J..(2021).Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice.Proceedings of the National Academy of Sciences of the United States of America,118(4).
MLA	Hanna C.C.,et al."Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice".Proceedings of the National Academy of Sciences of the United States of America 118.4(2021).