Periodic Reporting for period 2 - 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: 2021-08-01 to 2022-12-31
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 (PRD 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 praziquantel (PZQ). However, repeated treatment is needed for curative parasite clearance. 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 costly6 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 major objectives of the VASA project are to:
1. Assess the safety/immunogenicity of SchistoShield® in a Phase I clinical study in healthy adults from Africa;
2. Refine and develop a female worm schistosome human challenge model
3. To identify correlates of protection, innate and adaptive immune signatures, gene expression and the role of antibodies in the prevention/control of Schistosoma infections;
4. Foster a global consortium to advance research on schistosomiasis disease burden, vaccines and address downstream access constraints in resource-poor settings
The mainstay of schistosomiasis control is preventative and therapeutic administration of the anthelminthic praziquantel (PZQ). However, repeated treatment is needed for curative parasite clearance. 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 costly6 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 major objectives of the VASA project are to:
1. Assess the safety/immunogenicity of SchistoShield® in a Phase I clinical study in healthy adults from Africa;
2. Refine and develop a female worm schistosome human challenge model
3. To identify correlates of protection, innate and adaptive immune signatures, gene expression and the role of antibodies in the prevention/control of Schistosoma infections;
4. Foster a global consortium to advance research on schistosomiasis disease burden, vaccines and address downstream access constraints in resource-poor settings
The VASA project began in June 2019 and has been earnestly at work to set the groundwork for achieving the project objectives as a whole. In the first project period, the VASA consortium set the stage for a multi-disciplinary, international research collaboration that aims to advance development of schistosomiasis vaccines and improve the understanding of schistosomiasis disease burden in resource-limited settings. The consortium assembled various boards such as the Scientific Advisory Group and Ethics Advisory Board to provide scientific oversight to the project, and developed overall project management, data management, and monitoring and evaluation plans.
During the 2nd project period, the VASA consortium made substantial progress towards achieving overall project objectives, disseminating research highlights, and generating valuable research data. With much of the foundational groundwork laid during the 1st project period, the 2nd project period began in August 2021 with four active studies—the controlled human infection study led by Leiden, the cost-of-illness study led by the International Vaccine Institute (IVI), the sero-epidemiology study in Burkina Faso led by the University of Ouagadougou, and the sero-epidemiology study in Madagascar led by the University of Antananarivo. Over the course of this project period, all four of these studies completed their planned study activities, marking the successful conclusion of these work packages. The timely achievement of these studies is a testament to the hard work and collaboration of the VASA partners, and the study results will be disseminated through peer-reviewed publications, scientific conferences, and more.
Other VASA studies were activated during this project period, namely the schistosomiasis vaccine cost-effectiveness analysis, led by the IVI, and the immune signatures identification study led by the Texas Tech University Health Sciences Center. These work packages carried out preparatory activities such as study protocol standardization and SOP development, and we expect to see further progress in the next project period.
During the 2nd project period, the VASA consortium made substantial progress towards achieving overall project objectives, disseminating research highlights, and generating valuable research data. With much of the foundational groundwork laid during the 1st project period, the 2nd project period began in August 2021 with four active studies—the controlled human infection study led by Leiden, the cost-of-illness study led by the International Vaccine Institute (IVI), the sero-epidemiology study in Burkina Faso led by the University of Ouagadougou, and the sero-epidemiology study in Madagascar led by the University of Antananarivo. Over the course of this project period, all four of these studies completed their planned study activities, marking the successful conclusion of these work packages. The timely achievement of these studies is a testament to the hard work and collaboration of the VASA partners, and the study results will be disseminated through peer-reviewed publications, scientific conferences, and more.
Other VASA studies were activated during this project period, namely the schistosomiasis vaccine cost-effectiveness analysis, led by the IVI, and the immune signatures identification study led by the Texas Tech University Health Sciences Center. These work packages carried out preparatory activities such as study protocol standardization and SOP development, and we expect to see further progress in the next project period.
VASA will support and augment 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 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 will be scheduled 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 Sm-p80.
• Data from the human challenge model and non-human primate model of infection and disease will help identify immune markers and potential correlates of protection.
• Policymakers and opinion leaders of early adopter countries to identify data requirements for serious policy deliberations on the introduction of this vaccine into public health programs.
• Gavi and Ministries of Health as the cost-effectiveness data will be used to guide and support the introduction of schistosomiasis vaccines. The transferability of results and overall acceptance is a major component of VASA.
• Research groups interested in assessing the public health impact of Sm-p80-based schistosomiasis vaccine beyond the VASA program (e.g. reduction of resistance, complications and hospitalizations).
• Future vaccine manufacturers incl. DCVMs of Sm-p80-based vaccine as VASA will assess vaccine safety and effectiveness in the African setting.
VASA data collected is valuable for and relevant to:
• The acceleration of the schistosomiasis vaccine Sm-p80.
• Data from the human challenge model and non-human primate model of infection and disease will help identify immune markers and potential correlates of protection.
• Policymakers and opinion leaders of early adopter countries to identify data requirements for serious policy deliberations on the introduction of this vaccine into public health programs.
• Gavi and Ministries of Health as the cost-effectiveness data will be used to guide and support the introduction of schistosomiasis vaccines. The transferability of results and overall acceptance is a major component of VASA.
• Research groups interested in assessing the public health impact of Sm-p80-based schistosomiasis vaccine beyond the VASA program (e.g. reduction of resistance, complications and hospitalizations).
• Future vaccine manufacturers incl. DCVMs of Sm-p80-based vaccine as VASA will assess vaccine safety and effectiveness in the African setting.