Monday, 2 March 2020 from 4:00 pm in LT2, School of Chemistry  [Map] Refreshments to follow this lecture. (Postgraduate seminar)

Mr Cameron Hanna, School of Chemistry, The University of Sydney

[Email: chan8235@uni.sydney.edu.au ]

Host:  Professor Richard Payne

Abstract: 

Synthesis and Evaluation of Conjugate Vaccines for Tuberculosis

Cameron C. Hanna^a, Anneliese A. Ashhurst^b, Joshua W. C. Maxwell^a, Warwick J. Britton^b, Richard J. Payne^a

^aSchool of Chemistry, The University of Sydney, Australia

^bTuberculosis Research Program Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW 2050, Australia

Mycobacterium tuberculosis (M. tb), the etiological agent of tuberculosis (TB), causes an estimated 1.8 million deaths worldwide annually. Alarmingly, approximately one quarter of the world’s population is infected with M. tb. The development of an efficacious vaccine remains the major goal of the global End TB Strategy. Despite significant research effort, no new vaccines have been approved for use in humans since the introduction of the Bacillus Calmette-Guérin (BCG) vaccine in 1908. While the BCG vaccine is effective at protecting children from severe and disseminated TB, it does not provide protection for adults, especially those who are immunocompromised. Extensive research has shown that peptide or protein-based subunit vaccines can generate significant protection and enhancement of immune responses can be achieved through covalent conjugation of immunostimulatory molecules (adjuvants) to peptide or protein antigens to generate self-adjuvanting vaccines. Here, the development of new self-adjuvanting vaccines targeted against M. tb infection are described. Conjugate vaccines based on TB-associated antigens fused to Mincle- and TLR-agonists were synthesised through a combination of solution and solid-phase chemistry. In each case, vaccine candidates were evaluated both in vitro and in vivo to probe their activity and efficacy, and in many cases showed strong protection against M. tb challenge in murine models.