Professor of Vaccinology and Translational Medicine, Wellcome Trust Senior Fellow
My research interests include studies of vaccine-induced malaria immunity as well as the optimisation of antibody induction by subunit vaccines against the blood-stage of malaria infection.
In recent years, we have developed simian adenovirus (ChAd63) and MVA viral vectored vaccines targeting two major candidate antigens from the human malaria parasite P. falciparum (MSP1 and AMA1) and a leading candidate antigen (PvDBP) from P. vivax. We have demonstrated potent and effective T cell and antibody immunogenicity in preclinical models and have now translated these findings into a series of Phase I/IIa clinical vaccine trials funded by the MRC and EMVDA. The aims of this on-going clinical work are to assess the safety, immunogenicity and protective efficacy of these new vaccines in human volunteers. These studies provide an opportunity to better understand how vaccine-induced responses can protect against malaria infection in humans, and also how exposure to the parasite can modulate immunity. We have a particular interest in B cell clinical immunology and the identification of targets of antibody-mediated immunity. These studies of malaria-exposed volunteers in Oxford are also complemented by similar immunological studies in individuals who are naturally-exposed to malaria in Africa through our collaboration with the KEMRI-Wellcome Institute in Kilifi, Kenya.
More recently, our preclinical vaccine development work has focussed on the identification of improved antigen targets within the blood-stage merozoite parasite. We have established new protein vaccine production platforms that, along with viral vectored delivery, are enabling the generation of a whole new range of vaccines. To-date we have identified the PfRH5 antigen as the first reported target in the P. falciparum merozoite that is highly susceptible to broadly-neutralising vaccine-induced antibodies. This on-going programme of work is now aiming to define further antigens from the malaria genome and new target antigen combinations that should prove to be more successful in inducing protective efficacy against malaria by subunit vaccination in humans. In conjunction we are also undertaking studies to look at the utility of deploying protein-in-adjuvant and viral vectored vaccines in combination immunisation regimes, alongside research focusing on novel vaccine adjuvants. We are currently progressing viral vectored vaccines as well as a protein vaccine based on PfRH5 to Phase I/IIa clinical trials.
For a full list of publications click here.
Low immunogenicity of malaria pre-erythrocytic stages can be overcome by vaccination.
Müller K. et al, (2021), EMBO molecular medicine, 13
Low Adenovirus Vaccine Doses Administered to Skin Using Microneedle Patches Induce Better Functional Antibody Immunogenicity as Compared to Systemic Injection.
Flynn O. et al, (2021), Vaccines (Basel), 9
Mapping Gene-by-Gene Single-Nucleotide Variation in 8,535 Mycobacterium tuberculosis Genomes: a Resource To Support Potential Vaccine and Drug Development.
Papakonstantinou D. et al, (2021), mSphere, 6
Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum
Milne K. et al, (2021), eLife, 10
Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation
Rahikainen R. et al, (2021), Angewandte Chemie International Edition, 60, 321 - 330