Advancing vaccine development Vaccine development is a lengthy and costly process largely dependent on trial and error. Better tools are needed to evaluate vaccine effectiveness and correlate it with immunity particularly for those diseases for which immune responses conferring protective immunity are unknown, such as malaria. Health © Thinkstock Despite many years of research, it is still unclear what immune responses need to be induced in order to prevent malaria. As a result, most efforts in vaccine development have depended on trial and error approaches. It is widely accepted that surrogate biomarkers of immunity would significantly expedite clinical vaccine development and help eliminate non-viable candidates earlier in the pipeline. The understanding of the mechanisms conferring protection against malaria and the identification of biomarkers would shorten vaccine trial duration by offering measurements for efficacy that would guide future vaccine design. In this context, scientists on the EU-funded SYSMALVAC (Identifying correlates of protection to accelerate vaccine trials: systems evaluation of two models of experimentally-induced immunity to malaria) project set out to investigate the immune mechanisms that confer protection against malaria and to identify signatures of protection. To achieve this, they combined omics technologies with systems biology approaches. SYSMALVAC brought together researchers working on the two most efficient malaria vaccination strategies to date, namely the RTS,S vaccine that has recently completed a Phase III trial and has received positive scientific opinion by the European Medicines Agency, and the chloroquine chemoprophylaxis with Plasmodium falciparum sporozoites (CPS) approach. Both strategies have shown consistent protection in field trials and under experimental conditions. Scientists analysed transcriptomic profiles and immunological read-outs among human volunteers following immunisation, and the data was integrated into an artificial intelligence-based analytical tool. Over 1,700 proteins were mapped in a protein interaction network of human immune responses triggered by malaria. Interpretation of this network helped unveil the main physiological processes leading to protection in the RTS,S vaccine and CPS immunisation. The identified biomarkers were further refined and validated in a non-human primate model of experimentally induced immunity. Long term, the deliverables and insight generated during SYSMALVAC will lead to the development of an immunological platform for evaluating vaccine efficacy while reducing the duration and cost of such trials. Keywords Vaccines, systems biology, immunity, malaria, biomarkers, transcriptomics, computational models, protection
