Recently, the malaria burden was successfully reduced as a result of scale-up of preventive and treatment measures. Nevertheless, new tools, such as vaccines, are urgently needed. This is especially true given parasites are developing resistance to existing malaria drugs, and mosquitoes are developing resistance to insecticides.
Malaria vaccines are potential new tools in combating malaria by targeting several different stages of the parasite lifecycle to prevent infection and clinical disease, or to block malaria transmission.
Swiss TPH has a significant role in the research and development of new malaria vaccines, contributing across the whole development pathway: from discovery, to preclinical studies, and through to human clinical testing in both early and late studies with many African collaborators. This includes studies at the Clinical Trial Research Unit in Bagamoyo arm of the Ifakara Health Institute.
Several Swiss TPH malaria vaccine experts are members of review committees assessing malaria vaccines, and additionally, research groups at Swiss TPH have provided evidence, such as cost-effectiveness analysis, to decision making boards.
Using this unique opportunity of a multi-center phase III clinical trial in a two age cohorts of pediatric populations, we perform in depth immune-profiling analyses towards understanding RTS,S mode of action, beyond the measurement of anti-CSP repeat IgG titers. SwissTPH contributes to this study by analyzing sera/plasma and PBMC samples collected from 350 children in Bagamoyo, Tanzania, over a time frame of 32 months using multiplex and multi-parametric immunological techniques developed specifically for this study.
Swiss TPH has a leading role in assessing the health impact and cost-effectiveness of different malaria vaccines beyond clinical studies. The work involves using clinical trial data with mathematical and statistical models. The model-based analysis considers the role of vaccines in addition to existing control tools, and the role of new malaria vaccines in the future. The work takes into account contextual factors such as realistic coverage of immunization, target age groups and the distributions of malaria transmission intensities.
A promising concept of malaria vaccines are reconstituted influenza virosomes which display synthetic peptides of P. falciparum target antigenes on their surface. Recently, a new formulation incorporating two synthetic peptides has been demonstrated safety, immunogenicity and pilot efficacy in humans. However, we assume that a highly effective malaria subunit vaccine has to incorporate more than two components. Goal of this project is to develop additional peptide mimetics derived from the novel blood stage antigens CyRPA and RH5 and to evaluate their protective efficacy in an innovative P. falciparum infection mouse model.
Link to Project
Currently, more than 20 malaria vaccines candidates are being evaluated at various institutes world-wide, with one vaccine having completed Phase 3 Clinical studies, the malaria vaccine RTS,S/AS01, also known as Mosquirix. RTS,S received a positive scientific opinion from the European Medicines Agency and in early 2016 the World Health Organization recommended further implementation studies in Africa to assess its impact on mortality and the ability of immunization programmes to achieve four doses in children. Swiss TPH was integrally involved with partners in the Phase 3 and earlier clinical studies of RTS,S.
In addition, Swiss TPH led a multi-institute study, that predicted the public health impact and cost-effectiveness of the vaccine in sub-Saharan Africa when used in addition to high coverage of vector control. The researchers found that over a 15 year time horizon in moderate to high transmission settings, an average of 116,500 cases of clinical malaria disease and 484 deaths would be averted for every 100,000 children vaccinated under a four-dose schedule [more]. This work further contributed scientific evidence considered by the World Health Organization and Gavi, the vaccine alliance, in their decision making on use and funding.