Antigen presentation from malaria infected liver cells – identifying better CD8+ T cell antigens
Senior Immunologist and Insectary Manager
While traditional vaccination with heat-killed or attenuated vaccines has proved highly effective against pathogens controlled by neutralising antibodies, no vaccine has yet been licensed against pathogens in which cell mediated immunity plays an important role. Viral vaccines have shown a remarkable capacity to induce and boost T cells responses and are therefore the primary focus for our development of vaccines against malaria, influenza and tuberculosis. The ability of Adenovirus vectors to induce both T cells and antibodies, has prompted their use as a vaccine platform for use against emerging and re-emerging diseases.
Following completion of my PhD studies at the University of Sydney investigating CD4+ T cell activation, I joined the Jenner Institute in 2006 to apply my knowledge of T cells to study the immune response induced by viral vectored vaccines. Over the years I have investigated molecular adjuvants, vaccination regimens, new Adenovirus vectors and compared vaccine platforms for their ability to induce and boost the immune response, whilst also testing the efficacy of these vaccines in various disease models. The translational focus of the Jenner Institute has enabled me to follow these approaches from the early preclinical studies through to human clinical trials.
My research focuses on the type of T and B cell responses induced following vaccination in terms of effector capacity (cytokines and antibody isotypes/subclasses), phenotype (effector/memory) and organ specificity (tissue resident T and B cells). I am also interested in understanding the role of antigen and inflammatory signals in the induction and maintenance of T and B cell responses. This is complemented by work using T cell based assay and transgenic malaria parasites to investigate the underlying biology behind antigen processing and presentation from malaria-infected hepatocytes. The overall goal of my work is to identify more efficacious antigens and vaccination regimens which could be translated to the clinic.
The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies.
Spencer AJ. et al, (2022), EBioMedicine, 77
Detection and Quantification of Antibody to SARS CoV 2 Receptor Binding Domain provides enhanced Sensitivity, Specificity and Utility.
Rosadas C. et al, (2022), J Virol Methods
Deep immune phenotyping and single-cell transcriptomics allow identification of circulating TRM-like cells which correlate with liver-stage immunity and vaccine-induced protection from malaria
EWER K., (2022), Frontiers in Immunology
Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002)
EWER K. et al, (2021), The Lancet
Ultra-low dose immunization and multi-component vaccination strategies enhance protection against malaria in mice.
Collins KA. et al, (2021), Sci Rep, 11