Mucosal Vaccination with a Self-Adjuvanted Lipopeptide Is Immunogenic and Protective against Mycobacterium tuberculosis

Journal of Medicinal Chemistry
Anneliese S AshhurstRichard J Payne

Abstract

Tuberculosis (TB) remains a staggering burden on global public health. Novel preventative tools are desperately needed to reach the targets of the WHO post-2015 End-TB Strategy. Peptide or protein-based subunit vaccines offer potential as safe and effective generators of protection, and enhancement of local pulmonary immunity may be achieved by mucosal delivery. We describe the synthesis of a novel subunit vaccine via native chemical ligation. Two immunogenic epitopes, ESAT61-20 and TB10.43-11 from Mycobacterium tuberculosis (Mtb), were covalently conjugated to the TLR2-ligand Pam2Cys to generate a self-adjuvanting lipopeptide vaccine. When administered mucosally to mice, the vaccine enhanced pulmonary immunogenicity, inducing strong Th17 responses in the lungs and multifunctional peripheral T-lymphocytes. Mucosal, but not peripheral vaccination, provided substantial protection against Mtb infection, emphasizing the importance of delivery route for optimal efficacy.

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Citations

Jun 21, 2020·Vaccines·Céline LemoineAnita Milicic
Jan 21, 2021·Proceedings of the National Academy of Sciences of the United States of America·Cameron C HannaRichard J Payne
Dec 17, 2019·Journal of the American Chemical Society·Timothy S ChisholmRichard J Payne

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