Professor Dr. James Triccas

COVID-19 and tuberculosis (TB) are the top two leading infectious causes of death globally. Existing COVID-19 vaccines have had a remarkable impact on controlling the pandemic in certain countries, yet global vaccine access and affordability remain critical issues. The limited efficacy of the existing BCG vaccine contributes to the inability of current programs to adequately control TB. For our TB vaccine program, we have focussed on developing mucosal vaccines able to provide long lasting protection against infection in the lung. This includes subunit vaccines incorporating antigens from active and latent stages of infection, formulated with adjuvants that enhances immune cell recruitment to the vaccination site with minimal inflammation. Our lead candidate, CysVac2Advax, incorporates the fusion TB antigen CysVac2, together with the polysaccharide adjuvant delta inulin (Advax). In animal models pulmonary administration of CysVac2Advax results in the early recruitment and activation of a diverse diversity of innate immune cell types. CysVac2Advax-mediated protection was associated with the induction of lung-resident, antigen-specific memory CD4+ T cells that expressed IL-17; these cells were identified as the key mediator of vaccine efficacy, as blocking their function reduced phagocyte influx and ablated vaccine-induced protection. These findings suggest that tuberculosis vaccines such as CysVac2Advax that are capable of eliciting Th17 lung-resident memory T cells are promising candidates for progression to human trials.

Our COVID vaccine program employs stabilised, trimeric spike antigens from SARS-CoV-2 Variants of Concern (VOCs), developed by ExcellGene in an optimized, scalable and chemically-defined production process. When combined with different delivery platforms, these antigens demonstrate strong and persistent immunity in multiple animal models, notably the induction of high-titre and broadly neutralising antibodies against SARS-CoV-2 VOCs, including Omicron. Further, vaccines incorporating these trimeric spike antigens induced variant-specific protective immunity against both homologous/heterologous virus challenge in hamsters. Our data suggest that adjuvanted spike protein combinations could constitute safe, affordable, and mass-manufacturable COVID-19 vaccines for global distribution.