Dr Simon Draper

Research

The development of a highly effective malaria vaccine remains an important but elusive goal. To date, candidate blood-stage and transmission-blocking malaria vaccines have been based almost exclusively on protein-in-adjuvant formulations. However, despite extensive efforts by a number of excellent groups, these technologies have sadly shown limited success in clinical settings.

My early research established that a specific viral vectored immunisation regime, namely a recombinant adenovirus prime followed by a recombinant MVA poxvirus boost, is an effective means of inducing strong antibody responses. These data were contrary to the common perception at the time that viral vectored vaccines were only useful for inducing strong cellular immune responses against a transgene. Importantly, using these vectors expressing the blood-stage malaria antigen merozoite surface protein 1 (MSP1), we were able to show protective efficacy against blood-stage malaria infection in pre-clinical models. This protection was antibody-mediated, and on a par with the best previous studies using multiple immunisations of recombinant protein-in-adjuvant vaccines. Moreover, unlike protein vaccines which do not induce strong cellular responses, this viral vectored immunisation regime also induces potent CD8+ T cell responses, which are partially effective against the liver-stage parasite which expresses MSP1 late in development within infected hepatocytes. This was the first demonstration that protective multi-stage immunity against liver- and blood-stage malaria can be induced by using only two immunisations and a single target antigen.
Since this early work, my research interests have expanded to include studies of vaccine-induced malaria immunity as well as the continued optimisation of antibody induction by subunit vaccines against blood-stage, and more recently the mosquito-stage, of malaria infection.

In recent years, we have developed simian adenovirus (AdCh63) and MVA viral vectored vaccines targeting two major candidate antigens from the human malaria parasite P. falciparum (MSP1 and AMA1), and have demonstrated potent and effective T cell and antibody immunogenicity in pre-clinical models. We have translated these findings into Phase I/IIa clinical vaccine trials funded by the MRC and EMVDA. The aims of this 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 cells and how antibodies interact with immune cells in humans via Fc-receptors. 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.

My research group is also utilising the viral vectored vaccine delivery platform to screen blood- and mosquito-stage antigens for effective antibody induction. In 2002, the genome of P. falciparum was reported, highlighting the existence of over 5,000 genes. However, despite this genomic success, seven years later the malaria vaccine community has made little in road into this wealth of information, and indeed no systematic analysis of the utility and efficacy of so many potential vaccine candidate antigens has been reported. This programme of work is thus aiming to define new target antigen combinations that may prove to be more successful in inducing protective efficacy against malaria by subunit vaccination in humans. 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.

Key Publications

Draper, S. J., Biswas S., Spencer A. J., Remarque E. J., Capone S., Naddeo M., Dicks M. D. J., Faber B. W., de Cassan, S. C., Folgori A., Nicosia A., Gilbert S. C., and Hill A. V. S. (2010). Enhancing blood-stage malaria subunit vaccine immunogenicity in rhesus macaques by combining adenovirus, poxvirus and protein-in-adjuvant vaccines. J Immunol 185 7583-95. [PubMed]

Douglas, A. D., deCassan, S. C., Dicks, M. D. J., Gilbert, S. C., Hill, A. V. S., and Draper, S. J. (2010). Tailoring subunit vaccine immunogenicity: maximizing antibody and T cell responses by using combinations of adenovirus, poxvirus and protein-adjuvant vaccines against P. falciparum MSP1. Vaccine 28:7167-78. [PubMed]

Goodman, A. L., Epp, C., Moss, D., Holder, A. A., Wilson, J. M., Gao, G. P., Long, C. A., Remarque, E. J., Thomas, A. W., Ammendola, V., Colloca, S., Dicks, M. D. J., Biswas, S., Seibel, D., van Duivenvoorde, L. M., Gilbert, S. C., Hill, A. V. S., and Draper, S. J. (2010). New candidate vaccines against blood-stage P. falciparum malaria: simian adenoviral vectors expressing an optimized antigen based on MSP-1. Infect Immun 78-4601-12. [PubMed]

Goodman, A. L., and Draper, S. J. (2010). Blood-stage malaria vaccines – recent progress and future challenges. Ann Trop Med Parasitol 104:189-211. [PubMed]

Draper, S. J., and Heeney, J. L. (2010). Viruses as vaccine vectors for infectious diseases and cancer. Nat Rev Microbiol 8:62-73. [PubMed]

Hill, A. V. S., Reyes-Sandoval, A., O’Hara, G. A., Ewer, K., Lawrie, A., Goodman, A. L., Nicosia, A., Folgori, A., Colloca, S., Cortese, R., Gilbert, S. C., and Draper, S. J. (2010). Prime-boost vectored malaria vaccines: progress and prospects. Hum Vaccin 6:78-83. [PubMed]

Davies, M. N., Bayry, J., Tchilian, E. Z., Vani, J., Shaila, M. S., Forbes, E. K., Draper, S. J., Beverley, P. C., Tough, D. F., and Flower, D. R. (2009). Toward the in silico discovery of vaccine adjuvants: coupling virtual screening and in vitro analysis of antagonist binding to human and mouse CCR4 receptors. PLoS One 4:e8084. [PubMed]

Draper, S. J., Goodman, A. L., Biswas, S., Forbes, E. K., Moore, A. C., Gilbert, S. C., and Hill, A. V. S. (2009). Recombinant viral vaccines expressing merozoite surface protein-1 induce antibody- and T cell-mediated multistage protection against malaria. Cell Host Microbe 5:95-105. [PubMed]

Draper, S. J., Moore, A. C., Goodman, A. L., Long, C. A., Holder, A. A., Gilbert, S. C., Hill, F., and Hill, A. V. S. (2008). Effective induction of high-titer antibodies by viral vector vaccines. Nat Med 14:819-821. [PubMed]

Sridhar, S., Reyes-Sandoval, A., Draper, S. J., Moore, A. C., Gilbert, S. C., Gao, G. P., Wilson, J. M., and Hill, A. V. S. (2008). Single-dose protection against Plasmodium berghei by a simian adenovirus vector using a human cytomegalovirus promoter containing intron A. J Virol 82:3822-3833. [PubMed]

Bayry, J., Tchilian, E. Z., Davies, M. N., Forbes, E. K., Draper, S. J., Kaveri, S. V., Hill, A. V. S., Kazatchkine, M. D., Beverley, P. C., Flower, D. R., and Tough, D. F. (2008). In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination. Proc Natl Acad Sci U S A 105:10221-10226. [PubMed]

Win, T. Z., Draper, S. J., Read, R. L., Pearce, J., Norbury, C. J., and Wang S. W. (2006). Requirement of fission yeast Cid14 in polyadenylation of rRNAs. Mol Cell Biol 26:1710-21. [PubMed]

Moore, A. C., Gallimore, A., Draper, S. J., Watkins, K. R., Gilbert, S. C., and Hill, A. V. S. (2005). Anti-CD25 antibody enhancement of vaccine-induced immunogenicity: increased durable cellular immunity with reduced immunodominance. J Immunol 175:7264-73. [PubMed]