Discussion

Plasmodium falciparum malaria affects 200-300 million people annually, resulting in the death of about 0.5 million individuals. Another species of malaria parasite, P. vivax, also causes severe and relapsing malaria illness, but less mortality. P. vivax is more geographically widespread than P. falciparum, and is found largely in South America and South-East Asia. Thus, despite increasing implementation of control measures, the burden of malarial death and disease remains far too high. The most advanced subunit vaccine against P. falciparum, called RTS,S/AS01, has shown modest short-term efficacy against clinical disease in young children, whilst no effective vaccine exists for P. vivax. More recently, calls have been made for a second generation vaccine to exert 75% efficacy over two years against both species of parasite. If this ambitious rhetoric is to be realised, new approaches to malaria vaccine design are required. Vaccines against the parasite’s asexual blood-stage have the potential to complement RTS,S/AS01, and reduce mortality, morbidity and transmission of malaria, however such a vaccine has proved elusive. Recently, we have developed next-generation vaccines targeting the reticulocyte-binding protein homologue 5 from P. falciparum (PfRH5) and the Duffy-binding protein from P. vivax (PvDBP), both of which mediate essential invasion pathways into the human red blood cell. Critical to this work has been the elucidation of how human antibody responses are able to neutralise parasite invasion to guide rational vaccine design, coupled with human experimental studies. This talk will describe our on-going work and present data from our most recent Phase I/II clinical trials both in the UK and Africa.