Periodic Reporting for period 3 - VASA (Vaccine Against Schistosomiasis for Africa. A Phase I clinical study of the SchistoShield® anti-schistosomiasis vaccine in adults in endemic areas of sub-Saharan Africa)
Reporting period: 2023-01-01 to 2024-05-31
The VASA project addresses the overall objective of bridging the gap between preclinical and early clinical development of vaccines against schistosomiasis, one of the highest burden neglected parasitic disease in sub-Saharan Africa (sSA). Schistosomiasis is a poverty-related neglected disease and a significant cause of morbidity for an estimated 200 million people, with an additional 779 million individuals at risk for infection in 79 countries. Of deaths caused by parasites, schistosomiasis ranks second only to Plasmodium falciparum malaria, being the cause of death for an estimated 280,000 people annually in sSA alone.
The mainstay of schistosomiasis control is preventative and therapeutic administration of the anthelminthic PZQ. However, repeated treatment is needed for curative parasite clearance, which is challenging in hard-to-reach areas where schistosomiasis burden is highest. A single infection does not prevent future infection; as such, the cost-effectiveness of mass-treatment programs is compromised when reinfection is common. In order to combat the schistosomiasis burden, large-scale prevention strategies, such as mass vaccination campaigns, that complement treatment programs, are necessary. According to the WHO, target groups for large-scale, periodic treatment include school-aged children and adults at high risk (e.g. fishermen, farmers, irrigation workers and other persons who have increased contact with infested water) or entire communities living in highly endemic areas. Periodic PZQ treatment has shown to reduce clinical symptoms; however, there remains a gap between those who require and those who receive treatment. According to a 2015 estimate, only 28.2% of overall cases requiring treatment actually received care. An alternative or supplementary control method is the reduction of intermediate snail hosts using molluscicides, but this is even more challenging and costly, since frequent application of molluscicides is necessary and logistically challenging. Therefore, an efficacious and safe vaccine, giving long-lasting protection against all forms of schistosomiasis, will have a profound impact on infection control. In fact, “Science” ranked a schistosomiasis-vaccine among the top-10 most urgently needed vaccines. SchistoShield® (Sm-p80 plus GLA-SE) is one of the most promising vaccine candidates with documented efficacy against all major schistosome species studied in rodents and nonhuman primate studies.
The mainstay of schistosomiasis control is preventative and therapeutic administration of the anthelminthic PZQ. However, repeated treatment is needed for curative parasite clearance, which is challenging in hard-to-reach areas where schistosomiasis burden is highest. A single infection does not prevent future infection; as such, the cost-effectiveness of mass-treatment programs is compromised when reinfection is common. In order to combat the schistosomiasis burden, large-scale prevention strategies, such as mass vaccination campaigns, that complement treatment programs, are necessary. According to the WHO, target groups for large-scale, periodic treatment include school-aged children and adults at high risk (e.g. fishermen, farmers, irrigation workers and other persons who have increased contact with infested water) or entire communities living in highly endemic areas. Periodic PZQ treatment has shown to reduce clinical symptoms; however, there remains a gap between those who require and those who receive treatment. According to a 2015 estimate, only 28.2% of overall cases requiring treatment actually received care. An alternative or supplementary control method is the reduction of intermediate snail hosts using molluscicides, but this is even more challenging and costly, since frequent application of molluscicides is necessary and logistically challenging. Therefore, an efficacious and safe vaccine, giving long-lasting protection against all forms of schistosomiasis, will have a profound impact on infection control. In fact, “Science” ranked a schistosomiasis-vaccine among the top-10 most urgently needed vaccines. SchistoShield® (Sm-p80 plus GLA-SE) is one of the most promising vaccine candidates with documented efficacy against all major schistosome species studied in rodents and nonhuman primate studies.
During the 1st project period, the consortium assembled the Scientific Advisory Group and Ethics Advisory Board to provide scientific oversight, and developed overall project management, data management, and monitoring and evaluation plans.
During the 1st and 2nd project periods, the VASA consortium completed four critical studies on schistosomiasis—a female worm schistosome human challenge study led by LUMC, a cost-of-illness study led by the IVI, a sero-epidemiology study in Burkina Faso led by the U of Ouagadougou, and a sero-epidemiology study in Madagascar led by the U of Antananarivo. The sero-epidemiology and COI studies in the two schistosomiasis-endemic countries produced comprehensive data on disease burden and the true cost of disease on individuals and health systems. Preliminary analyses of the sero-epidemiology data have yielded valuable insights into age-of-infection, burden in rural versus urban communities, and risk factors. We expect that the results from these studies will be of great value to regional disease control programs, health policy makers, and other researchers. Manuscripts of study results are currently in development, and will be submitted for peer-review to open-access journals. Further, the results from the female worm schistosome human challenge study made significant advances in understanding the complex immunogenicity of schistosomiasis infection in humans. These results are now published in eBioMedicine (Koopman JPR et al., eBioMedicine, 2023).
The VASA consortium has also been active in the greater research and public health community. Together with the International Institute of Science and Technology of Burkina Faso, the VASA consortium organised an international symposium on neglected tropical diseases in November 2022. VASA partners presented preliminary results from the sero-epidemiology and COI studies to a diverse audience of researchers and stakeholders from the region.
During the most recent project period, the VASA consortium successfully initiated the Phase 1b clinical study of Sm-p80+GLA-SE vaccine in healthy adults in Burkina Faso and in Madagascar. This trial marks the first clinical study of the vaccine candidate in schistosomiasis endemic populations, and will assess safety and immunogenicity. The trial began study recruitment in Madagascar in November 2023 and in Burkina Faso in March 2024. Other non-clinical VASA studies continued in this project period, namely the schistosomiasis vaccine cost-effectiveness analysis, led by the IVI, and the immune signatures identification study led by the TTUHSC. These work packages carried out preparatory activities, and we expect to see further progress in the next period as samples and data become available. Once results are ready, we will follow the dissemination plan, including but not limited to presenting at stakeholder meetings, publishing peer-reviewed literature, and approaching country policy makers.
During the 1st and 2nd project periods, the VASA consortium completed four critical studies on schistosomiasis—a female worm schistosome human challenge study led by LUMC, a cost-of-illness study led by the IVI, a sero-epidemiology study in Burkina Faso led by the U of Ouagadougou, and a sero-epidemiology study in Madagascar led by the U of Antananarivo. The sero-epidemiology and COI studies in the two schistosomiasis-endemic countries produced comprehensive data on disease burden and the true cost of disease on individuals and health systems. Preliminary analyses of the sero-epidemiology data have yielded valuable insights into age-of-infection, burden in rural versus urban communities, and risk factors. We expect that the results from these studies will be of great value to regional disease control programs, health policy makers, and other researchers. Manuscripts of study results are currently in development, and will be submitted for peer-review to open-access journals. Further, the results from the female worm schistosome human challenge study made significant advances in understanding the complex immunogenicity of schistosomiasis infection in humans. These results are now published in eBioMedicine (Koopman JPR et al., eBioMedicine, 2023).
The VASA consortium has also been active in the greater research and public health community. Together with the International Institute of Science and Technology of Burkina Faso, the VASA consortium organised an international symposium on neglected tropical diseases in November 2022. VASA partners presented preliminary results from the sero-epidemiology and COI studies to a diverse audience of researchers and stakeholders from the region.
During the most recent project period, the VASA consortium successfully initiated the Phase 1b clinical study of Sm-p80+GLA-SE vaccine in healthy adults in Burkina Faso and in Madagascar. This trial marks the first clinical study of the vaccine candidate in schistosomiasis endemic populations, and will assess safety and immunogenicity. The trial began study recruitment in Madagascar in November 2023 and in Burkina Faso in March 2024. Other non-clinical VASA studies continued in this project period, namely the schistosomiasis vaccine cost-effectiveness analysis, led by the IVI, and the immune signatures identification study led by the TTUHSC. These work packages carried out preparatory activities, and we expect to see further progress in the next period as samples and data become available. Once results are ready, we will follow the dissemination plan, including but not limited to presenting at stakeholder meetings, publishing peer-reviewed literature, and approaching country policy makers.
VASA supports and enhances ongoing activities to enhance schistosomiasis control efforts while also advancing the understanding of schistosomiasis burden in sub-Saharan Africa. Data derived from the human challenge model, the sero-epidemiology studies, the investment case, and the Phase I studies will help the African countries make informed decision on potential vaccine introduction pathways for their high-risk populations. Further, the data from the two study sites will help pave the way for future Phase II, which is already funded by the Gates Foundation to be executed in 2025, and, eventually, large-scale Phase III studies for the Sm-p80 vaccine. Such discussions and results will be communicated to African NITAGs, WHO, UNICEF, Gavi and other relevant stakeholders during the two pan-African schistosomiasis stakeholder meetings budgeted in the proposal (see above). These have been twice in the course of the funding period in order to facilitate global dialogue within the schistosomiasis community and provide a forum for discussion and integration of current findings of VASA and other projects. Further, members of the VASA consortium members will work together with DCVMs to start technology transfer and to plan sustainable supply to meet forecasted demand. VASA data collected is valuable for and relevant to:
•The acceleration of the schistosomiasis vaccine Schistoshield®
•Data from the human challenge model will help identify immune markers and potential correlates of protection
•Policymakers and opinion leaders of early adopter countries for serious policy deliberations on the vaccine introduction
•Gavi and Ministries of Health as the cost-effectiveness data will be used to guide and support the introduction of schistosomiasis vaccines
•Research groups interested in assessing the public health impact of Sm-p80-based schistosomiasis vaccine beyond the VASA program
•Future vaccine manufacturers incl. DCVMs of Sm-p80-based vaccine Schistoshield® as VASA will assess vaccine safety and effectiveness in the African setting
•The acceleration of the schistosomiasis vaccine Schistoshield®
•Data from the human challenge model will help identify immune markers and potential correlates of protection
•Policymakers and opinion leaders of early adopter countries for serious policy deliberations on the vaccine introduction
•Gavi and Ministries of Health as the cost-effectiveness data will be used to guide and support the introduction of schistosomiasis vaccines
•Research groups interested in assessing the public health impact of Sm-p80-based schistosomiasis vaccine beyond the VASA program
•Future vaccine manufacturers incl. DCVMs of Sm-p80-based vaccine Schistoshield® as VASA will assess vaccine safety and effectiveness in the African setting