Could a synergistic approach give rise to more effective malaria vaccines?

In the largest study of its kind, researchers from Wellcome Trust Sanger Institute (Cambridge, UK) and their collaborators have uncovered five new malaria vaccine targets, suggesting that targeting multiple factors may lead to more effective vaccines.

Most attempts to produce vaccines focus on single target antigen. In this study, published recently in the Proceedings of the National Academy of Sciences, the researchers discovered five antigens involved in malaria erythrocyte invasion, an essential lifecycle step and the malaria parasite’s most vulnerable stage, which could be targets for future vaccine development.

The team screened 29 blood-stage antigens, raising rabbit antibodies against these and testing the subsequent antibodies on two strains of Plasmodium falciparum. Of the 29 antibodies tested, five were demonstrated to inhibit the parasite’s ability to invade red blood cells.

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Author, Gavin Wright from the Wellcome Trust Sanger Institute, commented: “Producing a successful vaccine against parasites is challenging because they are very complex organisms with many components, making it difficult to know which ones to target. By studying the parasite’s genome and working backwards, in a process known as reverse vaccinology, we have discovered five vaccine targets which, if combined, show promise for further development.”

The team went on to assess whether the antibodies they’d identified had any association with natural immunity in individuals. They discovered that although no single antibody appeared to correlate with protection in patients, combinations of the antibodies did protect against the plasmodium parasite, suggesting that targeting multiple antigens might be a good strategy.

To further confirm this, the team used video microscopy to assess the process at a cellular level, observing that the antibodies targeted different stages of entry and that pairing of these antibodies led to more effective inhibition of erythrocyte invasion.

These results were explained by author, Pietro Cicuta (University of Cambridge, UK): “Using video microscopy, we were able to see the different antibodies attacking the parasite at various stages as it attempted to invade red blood cells. These results give insight into a new, synergistic view of vaccine development. We believe a new vaccine would be the most effective if it put roadblocks at several points along the parasite’s path into the red blood cells.”

Lead author, Julian Rayner (Wellcome Trust Sanger Institute) concluded: “This study was only possible due to the scale of studying multiple vaccine targets, and the huge collaborative effort. By bringing together multiple areas of expertise, from genomics to large field studies of patients in Mali, and down to advanced video microscopy observing individual parasites, we have discovered several new vaccine targets that warrant further investigation. It’s a great example of collaborative international science and its potential impact.”

Sources: Bustamante LY, Powell GT, Lin Y et al. (2017) Synergistic malaria vaccine combinations identified by systematic antigen screening. Proc. Natl Acad. Sci. doi:10.1073/pnas.1702944114 (2017) (Epub ahead of print);


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