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.
This review summarizes the evidence that VSAs are important targets of NAI, discusses why VSA-based vaccines might be feasible despite the extensive intra- and interclonal variation of VSAs, and how vaccines based on this type of antigens fit into the current global strategy to reduce, eliminate, and eventually eradicate the burden of malaria.
Genome-wide approaches are now warranted to map the major genetic determinants of variable antibody isotype and subclass responses to malaria, alongside evaluation of their impact on infection and disease. Although plasma levels of IgG4 to malaria antigens are generally low, the exceptionally high heritability of levels of this subclass in children deserves particular investigation.
This case strongly supports the hypothesis that parasite surface proteins such as PfEMP1, A-type RIFIN or STEVOR are involved in interactions of infected erythrocytes with endothelial receptors mediating sequestration of mature asexual and immature sexual stages of P. falciparum. In contrast, multicopy gene families coding for B-type RIFIN and PfMC-2TM proteins may not be involved in sequestration, as these genes were transcribed in infected but not sequestered erythrocytes.
Over the past decade (2000 – 2009), there have been nine clinical trials of synthetic malaria peptide vaccines designed to target the pre-erythrocytic and erythrocytic stages of the Plasmodium falciparum parasite. The results of these clinical trials, while encouraging, have emphasized the critical roles of immunological assays, in particular functional assays, for the evaluation of potential vaccine candidates. Additional challenges include the need for potent adjuvants for the development of synthetic peptide vaccines that can effectively target multiple stages of the Plasmodium parasite.
It is widely believed that human malaria parasites infect only man as a natural host. However, earlier morphological observations suggest that great apes are likely to be natural reservoirs as well. To identify malaria parasites in great apes, we screened 60 chimpanzees imported into Japan.