The Jenner Institute, University of Oxford
Old Road Campus Research Building, Roosevelt Drive
Oxford, OX3 7DQ
|Principal areas of research:||Sporozoite-targeting malaria vaccines and rabies vaccines.|
I am an academic clinician and hold a Wellcome Trust Postdoctoral Fellowship for Clinicians (i.e. Career Development fellowship). My main interests are the development of antibody-inducing vaccines against the sporozoite stage of malaria and the development of a novel thermostable rabies vaccine.
In earlier work, I identified the potential of PfRH5 as an antigen capable of inducing highly potent strain-transcending neutralising antibodies against the disease causing blood-stage of Plasmodium falciparum and demonstrated that PfRH5-based vaccines could achieve in vivo protection against a virulent P. falciparum challenge. These vaccines are now in clinical trials.
Understanding of the mechanism of erythrocyte invasion by P. falciparum merozoites has yielded promising new vaccine targets like PfRH5. 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.
Many people do not realise that rabies kills around 50,000 people each year. One reason is that existing rabies vaccines require multiple doses, cold-chain storage and are moderately expensive. I am leading a project to manufacture and test in clinical trials an adenovirus-vectored rabies vaccine in a thermostable formulation. In pre-clinical studies, a single low dose of the vaccine achieves protection against rabies challenge for over two years. The thermostabilisation technology has potential to be applied to multiple human and veterinary vaccines, overcoming the challenges and cost of cold chain distribution. The vaccine aims to become a cheap, single-dose tool suitable for mass pre-exposure rabies prophylaxis.
Most candidate malaria vaccines targeting extracellular stages of the parasite require extremely high antibody concentrations to achieve efficacy. Recent clinical trials have shown that current adjuvant formulations are not capable of sustaining such levels for more than a few weeks. I have an interest in the development of protein subunit vaccine formulations capable of enhancing the long-term maintenance of high-level antibody titers.
For up to date information and publications list, please see my Google Scholar profile: http://tinyurl.com/sandydouglas.
Germinal centre B cell and T follicular helper cell responses to viral vector and protein-in-adjuvant vaccines, Chuan W, Hart M, Chui C, … Douglas AD, J. Immunol. 2016 Aug 15;197(4):1242-51. doi: 10.4049/jimmunol.1502472.
Douglas AD, Baldeviano GC, Lucas CM, Lugo-Roman LA et al, PfRH5 vaccine efficacy against heterologous strain blood-stage Plasmodium falciparum, Cell Host and Microbe, 2015 Jan 14;17(1):130-9. doi: 10.1016/j.chom.2014.11.017
KE Wright, KA Hjerrild, J Bartlett, AD Douglas, et al, Structure of malaria invasion protein RH5 with erythrocyte basigin and blocking antibodies, Nature, 2014 Aug 17. doi: 10.1038/nature13715.
Douglas AD, Williams AR, Knuepfer E, et al, Neutralization of Plasmodium falciparum merozoites by antibodies against PfRH5, J Immunol. 2014 Jan 1: 192(1):242-58, Williams AR, Douglas AD, Miura K, Illingworth JJ, et al.
Enhancing Blockade of Plasmodium falciparum Erythrocyte Invasion: Assessing Combinations of Antibodies against PfRH5 and Other Merozoite Antigens. PLoS Pathogens., 2012 Nov; 8(11):e1002991. doi: 10.1371/journal.ppat.1002991.
Douglas AD, Williams AR, Illingworth JJ, et al, The Blood-Stage Malaria Antigen PfRH5 is Susceptible to Vaccine-Inducible Cross-Strain Neutralizing Antibody, Nature Communications, 2011 Dec 20;2:601.
Douglas AD, Andrews L, Draper SJ, et al, Substantially reduced pre-patent parasite multiplication rates are associated with naturally acquired immunity to Plasmodium falciparum. J Infect Dis. 2011 May 1;203(9):1337-40.