Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice
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 Two vaccine construct...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 4 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
26.01.2021
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Subjects | |
Online Access | Get full text |
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Summary: | 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
Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam
Cys-SK
or Pam
Cys-SK
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
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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Author contributions: C.C.H., A.S.A., W.J.B., and R.J.P. designed research; C.C.H., A.S.A., D.Q., and J.W.C.M. performed research; C.C.H., A.S.A., J.W.C.M., and R.J.P. analyzed data; and C.C.H., A.S.A., W.J.B., and R.J.P. wrote the paper. 1C.C.H. and A.S.A. contributed equally to this work. Edited by Chi-Huey Wong, Academia Sinica, Taipei, Taiwan, and approved December 8, 2020 (received for review July 1, 2020) |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.2013730118 |