Synthetic protein conjugate vaccines provide protection against Mycobacterium tuberculosis in mice.
Proc Natl Acad Sci U S A
; 118(4)2021 01 26.
Article
in English
| MEDLINE | ID: covidwho-1387607
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Tuberculosis
/
Vaccines, Conjugate
/
Tuberculosis Vaccines
/
Mycobacterium tuberculosis
Type of study:
Observational study
Topics:
Vaccines
Limits:
Animals
Language:
English
Year:
2021
Document Type:
Article
Affiliation country:
PNAS.2013730118
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