After completing a PhD in molecular virology at the Pirbright Institute, I moved to the NDM in May 2012. Since then I have been working on Adeno and MVA viral vectored vaccine platform. Initially I worked in Prof. Sarah Gilbert’s group, at the Jenner Institute, on Chimp-Adeno and MVA viral vector modifications and the flu vaccine development programme and then moved to Prof. Ellie Barnes' group.
My research is primarily focussed on translational research in vaccinology and the current interests are on the development of a prophylactic Hepatitis C vaccine and a therapeutic Hepatitis B vaccine, using Chimpanzee-Adeno and MVA viral vector platform. Research interests, within our vaccine group, range from vaccine design, development, pre-clinical and clinical testing. Our vaccine group are also involved in the immunological assessment of Phase-I human clinical studies of the first generation HCV vaccines, owned by GSK.
Prophylactic Hepatitis C vaccine: Hepatits C virus (HCV), due to its high replication rate and lack of proof-reading activity of its RNA polymerase, is a diverse pathogen and there are 6 major genotypes and more than 80 subtypes. We have developed a second-generation prophylactic Hepatitis C vaccine, with the aim of inducing protection across different HCV genotypes, which could potentially overcome the limited cross reactivity of the first-generation HCV vaccine (which is based on a single genotype) that are now in Phase-II clinical testing in Baltimore and San Francisco. Currently we are conducting pre-clinical studies with the second-generation prophylactic Hepatitis C vaccine.
Therapeutic Hepatitis B vaccine: Highly effective prophylactic Hepatitis B vaccines are available, but they lack therapeutic effect on chronic hepatitis B. Two major issues with chronic hepatitis B are (1) the presence of persistently infected hepatocyte [due to the establishment of a mini-chromosomal form of HBV DNA, termed as cccDNA, within the nucleus of infected hepatocytes, which serves as a continuous source of new virus production] and (2) functionally exhausted HBV-specific CD8 T-cells, which fail to mount an effective anti-HBV response within a chronically HBV infected individual. A recent immuno-therapeutic proof of concept study, using a HBV-like woodchuck hepatitis virus, suggests that combining a vaccine that could elicit T-Cell response and an immuno-modulator (anti-PDL1) that could reverse the exhaustion, could potentially have a therapeutic effect (clearance of persistently HBV-infected hepatocytes) on chronic Hepatitis B. Moving down this path, we have generated a Chimpanzee-Adeno viral vector based hepatitis B vaccine, which could be used in combination with an immuno-modulators to device an immuno-therapy to overcome chronic hepatitis B. Currently we are testing this vaccine in pre-clinical studies.
Divergent memory responses driven by adenoviral vectors are impacted by epitope competition.
Colston JM. et al, (2019), Eur J Immunol, 49, 1356 - 1363
Prime-boost vaccination strategies using chimpanzee-adeno and MVA viral vectored vaccines encoding multiple HBV antigens (CPmutS) and class II invariant chain molecular adjuvants induces robust T-cell and anti-HBs antibody response in mice
Cargill T. et al, (2019), JOURNAL OF HEPATOLOGY, 70, E459 - E460
A novel chimpanzee adenoviral vectored HBV vaccine, encoding multiple HBV antigens with a shark invariant chain adjuvant, for use in HBV immunotherapy
Chinnakannan SK. et al, (2018), JOURNAL OF HEPATOLOGY, 68, S789 - S790
A pan-genotype HCV T cell vaccine, in a simian adenovirus vector, to target T cell epitopes conserved across multiple HCV genotypes
Donnison T. et al, (2018), JOURNAL OF HEPATOLOGY, 68, S800 - S801
The generation of a simian adenoviral vectored HCV vaccine encoding genetically conserved gene segments to target multiple HCV genotypes.
von Delft A. et al, (2018), Vaccine, 36, 313 - 321