Alexander (Sandy) Douglas
Henry Wellcome Building for Molecular Physiology
Alexander (Sandy) Douglas
DPhil, MRCP, DipPharmMed
Research Group Leader
I am a pharmaceutical physician and Wellcome Trust Career Development Fellow.
My main interests are the development of new antibody-inducing vaccines and breaking down the barriers to translation of new biological medicines into clinical trials. My group's work spans from protein biochemistry and virology (seeking to design new and improved vaccine antigens), through development of high-quality yet cost-effective biological manufacturing processes, to clinical trials.
VACCINE MANUFACTURING PROCESS DEVELOPMENT
My group led manufacturing scale-up of the University of Oxford COVID-19 vaccine candidate up to the point of transfer to AstraZeneca. This included the development of a novel and highly cost-effective large-scale manufacturing process, which is now underpinning global supply of the vaccine.
I am a Co-Investigator on the EPSRC funded Future Vaccine Manufacturing Research Hub (Vax-Hub)
Existing rabies vaccines require multiple doses, cold-chain storage and are moderately expensive: as a result they are not widely used in rabies-endemic areas, and 50,000 people die of rabies every year. I have developed and am leading clinical trials of an adenovirus-vectored rabies vaccine which aims to provide a cheap, single-dose tool suitable for mass pre-exposure rabies prophylaxis. This work is funded by an MRC DPFS award.
I have also recently received funding from the Wellcome Trust for a new project investigating the feasibility of development of a vaccine against Epstein Barr virus. Although most people are infected with EBV without suffering serious effects, it causes a substantial burden of cancers and may drive development of certain immune-mediated diseases, such as multiple sclerosis.
I previously identified the potential of PfRH5 as an antigen capable of inducing highly potent strain-transcending neutralising antibodies against the Plasmodium falciparum blood-stage and demonstrated that PfRH5-based vaccines could achieve in vivo protection against a virulent P. falciparum challenge. These vaccines are now in clinical trials.
PfRH5 was identified by investigating the mechanism of erythrocyte invasion by P. falciparum merozoites. Sporozoites are in many ways more attractive vaccine targets than merozoites, but understanding of the mechanism of sporozoite invasion into hepatocytes is poor. I am seeking to identify sporozoite ligands and host receptors required for this invasion process, with the aim of developing interventions to prevent infection by disrupting their interactions.
Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses
Barrett JR. et al, (2020), Nature Medicine
T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial
Ewer KJ. et al, (2020), Nature Medicine
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Voysey M. et al, (2020), The Lancet
Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial
Ramasamy MN. et al, (2020), The Lancet, 396, 1979 - 1993
Immunological considerations for SARS-CoV-2 human challenge studies
Douglas AD. and Hill AVS., (2020), Nature Reviews Immunology