Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice

Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: Proceedings of the National Academy of Sciences
Volume: 118
Number: 4
Page Range: e2013730118
Date: 2021
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.1073/pnas.2013730118
ISSN: 0027-8424
Date Deposited: 10 Jun 2021 06:10

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.

Hanna, Cameron C.
Ashhurst, Anneliese S.
Quan, Diana
Maxwell, Joshua W. C.
Britton, Warwick J.
Payne, Richard J.
Last Modified: 10 Jun 2021 06:10

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