Progress towards a broadly neutralizing vaccine against the asexual blood-stage of Plasmodium falciparum

Abstract

Event Abstract Back to Event Progress towards a broadly neutralizing vaccine against the asexual blood-stage of Plasmodium falciparum Alexander D. Douglas1*, Andrew R. Williams1, Joseph J. Illingworth1, Kathryn A. Hjerrild1 and Simon J. Draper1 1 University of Oxford, Jenner Institute, Nuffield Department of Medicine, United Kingdom There is a need for a more effective vaccine against P. falciparum than the current leading candidate, RTS,S. Vaccines against the parasite’s asexual blood-stage may reduce mortality, morbidity and transmission of malaria, but face problems of antigenic polymorphism and the apparent requirement for exceptionally high antibody levels to achieve protection. We recently reported that vaccines based upon the blood-stage merozoite antigen PfRH5 induce antibodies capable of strain-transcending in vitro growth inhibition activity (GIA). Here we will now describe cross-strain protection achieved by these vaccines in the stringent Aotus nancymaae non-human primate – P. falciparum challenge model, which correlates strongly with vaccine-induced pre-challenge GIA and total IgG anti-PfRH5 ELISA titres. This is the first example of clinically meaningful cross-strain protection of Aotus by a human-compatible blood-stage vaccine regime, and supports the strategy of vaccine selection using in vitro GIA. We will also describe work to characterise the mechanism of parasite neutralisation by anti-PfRH5 antibodies. This includes generation of novel monoclonal antibodies with neutralisation potency among the highest described for any anti-merozoite antibody, and mapping of minimal linear epitopes for two of these. We will present data which suggest that fine epitope specificity and interaction kinetics are more important determinants of neutralisation potency than ability to block the interaction between PfRH5 and its receptor, basigin. These data shed important insight on the mechanism of blood-stage malaria parasite neutralisation, and support the continued clinical development of PfRH5-based vaccines. Phase Ia clinical trials of PfRH5 vaccine candidates are due to commence in Oxford in 2014. Keywords: Malaria, Falciparum, Malaria Vaccines, PfRh5, Antibodies, viral vector vaccines Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Douglas AD, Williams AR, Illingworth JJ, Hjerrild KA and Draper SJ (2013). Progress towards a broadly neutralizing vaccine against the asexual blood-stage of Plasmodium falciparum. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00574 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Alexander D Douglas, University of Oxford, Jenner Institute, Nuffield Department of Medicine, Oxford, OX3 7DQ, United Kingdom, sandy.douglas@ndm.ox.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper Google Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper Google Scholar Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper PubMed Alexander D Douglas Andrew R Williams Joseph J Illingworth Kathryn A Hjerrild Simon J Draper Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.