The RTS,S/AS01E malaria vaccine candidate has recently entered phase 3 testing. Reaching this important milestone is the culmination of more than 20 years of research and development by GlaxoSmithKline and partners and collaborators. The vaccine has been developed to protect young children and infants living in sub-Saharan Africa against clinical and severe disease caused by Plasmodium falciparum infection.
Plasmodium chabaudi AS infection during early pregnancy results in midgestational embryonic loss in naive C57BL/6 mice. To define the immunopathogenesis of this malaria-induced pregnancy compromise, cytokine production in plasma, spleen, and placenta cell culture supernatants during the first 11 days of infection and gestation was studied. These results suggest that systemic and placenta-level proinflammatory antimalarial immune responses, in the absence of adequate and sustained counterregulatory mechanisms, contribute to pregnancy loss in this model.
The increasing P. vivax drug resistance and reports of severe and lethal cases, the relapsing parasite behavior and the existence of Plasmodium spp co-infections must prompt more investment and greater efforts for the development of P. vivax vaccine.
Subunit vaccines under development for malaria utilise a limited number of approaches to delivery.
Therefore, along with the efforts to advance the most promising vaccine formulations through the development pipeline, research is taking place into alternative methods for cheaper vaccine production and easy administration. This chapter will discuss some of these approaches, including transgenic plants and mammals as bioreactors for low cost vaccine production and alternative routes of vaccine delivery such as mucosal immunization.
In this review previous studies in rodents and primates of whole killed and attenuated blood stage vaccines, and recent work on the effect of genetically attenuated parasites on immunity in rodent models of blood stage immunity are discussed. The relationship between these findings and what is now known about protective immunity in human populations, specifically against the blood stages of the parasite lifecycle is discussed and recent findings from human experimental infection are be reviewed.
The difficulty of inducing protective immunity through antibodies against sporozoites led to efforts to assess vectored vaccines as a means of inducing protective T cell immunity against the malaria liver-stage parasite. Although DNA vectored vaccines used alone were poorly immunogenic and not protective, high levels of parasite clearance in the liver has been achieved with viral vectored vaccines used in heterologous prime-boost regimes.
Despite its small population and isolate location Papua New Guinea (PNG) with a malaria burden comparable to sub-Saharan Africa, its intense transmission of all 4 human Plasmodium species and an unrivalled combination of environmental and human variation offers unique perspectives on malaria vaccines.
Important progress has been made in the last years especially in sub-Saharan Africa, with the introduction of strategies to prevent malaria in pregnancy consisting of intermittent preventive treatment and insecticide treated nets. However, their coverage is still unacceptably low and malaria continues to demand a huge toll on pregnant women and their newborns. Thus, there is a need to explore other preventive strategies such as a vaccine against malaria, which combined with the current tools would maximise the protection efficacy.
Over the past ten years, EMVI has continually strived to maintain its main goal of accelerating the development of candidate malaria vaccines by facilitating the translational gap between promising experimental malaria vaccines and subsequent clinical trials in Europe and in Africa. By stimulating collaboration, cooperation, networking and joint integrated activities across various fields of research and diseases, and by facilitating the federation of research infrastructures, EMVI is acting today as a catalyst for tomorrow’s vaccines.