Synthesis and Evaluation of a Library of Self-Adjuvanting Peptide and Protein Vaccines against Mycobacterium tuberculosis  — ASN Events
  1. Schedule
  2. Poster Session 2 and Drinks
  3. Synthesis and Evaluation of a Library of Self-Adjuvanting Peptide and Protein Vaccines against Mycobacterium tuberculosis 

Synthesis and Evaluation of a Library of Self-Adjuvanting Peptide and Protein Vaccines against Mycobacterium tuberculosis  (#225)

Cameron Hanna 1
  1. University of Sydney, Sydney, NSW, Australia

Mycobacterium tuberculosis (Mtb), the aetiological agent of tuberculosis (TB), causes an estimated 1.8 million deaths worldwide annually.1 The development of an efficacious vaccine remains the major goal of the global End TB Strategy.1 Peptide or protein-based subunit vaccines offer potential as safe and effective generators of protection, and we and others have shown that enhancement of immune responses can be achieved through covalent conjugation of immunostimulatory molecules to the peptide or protein scaffold.2 We synthesised a library of self-adjuvanting TB vaccines containing either the Mtb associated ESAT-6(1-20) and TB10.4(3-11) peptides or a fully synthetic ESAT-6(1-95) protein conjugated to three different immunostimulatory adjuvants: Pam2Cys (TLR2/6 agonist), Pam3Cys (TLR2/1 agonist) or an immunomodulator derived from mycobacterial cord factor (Mincle agonist). When administered mucosally to mice, the Pam2Cys-ESAT6(1-20)TB10.4(3-11), Pam2Cys-ESAT6(1-95), and Pam3Cys-ESAT6(1-95) vaccines enhanced pulmonary immunogenicity, inducing strong Th17 responses in the lungs which provided substantial protection against Mtb infections.3 

  1. WHO, Global Tuberculosis Report. 2016.
  2. McDonald, D. M.; Hanna, C. C.; Ashhurst, A. S.; Corcilius, L.; Byrne, S. N.; Payne, R. J., ACS Chem. Biol. 2018, 13 (12), 3279-3285.
  3. Ashhurst, A.; McDonald, D.; Hanna, C.; Stanojevic, V.; Britton, W. J.; Payne, R. J. J. Med. Chem. 2019. Just accepted.