Periodic Reporting for period 1 - RIFTVAX (Clinical development of Rift Valley fever vaccines in endemic regions)
Okres sprawozdawczy: 2022-08-01 do 2024-01-31
Spread by a virus of the same name, Rift Valley fever (RVF) is transmitted by different species of mosquitoes (Aedes, Culex, Anopheles, and Mansonia) as well as blood feeding flies, often driven by climatic changes across Africa and parts of the Arabian Peninsula. It most commonly affects domesticated and livestock animals, such as cattle, sheep, goats, and camels, but can also cause illness in people. Although the disease is mostly mild in humans, it can cause a deadly haemorrhagic fever in 1-2% of cases.
Rift Valley fever happens pretty regularly in relatively small numbers, in Africa – and cases have also been reported in the Arabian peninsula. However, occasionally, there are large and very explosive outbreaks that have very large cases and numbers - the disease is estimated to have cost the region $300 million since RVF was first discovered, causing collapses in livestock markets which, at the time, made up the majority of national income for countries like Somalia.
Outbreaks usually start after rainy season, where we get mosquito blooms. The infected mosquitoes then bite animals and the animals bite humans, so we get a spread. At this time, we do not know where the reservoir of disease is, although it is most likely in wild animals. Since its first identification, outbreaks of Rift Valley fever have typically occurred in 4-15-year cycles and have been consistently linked with periods of surges in rainfall that occur as a result of the El Niño phenomenon. This is a climate pattern that describes the unusual warming of surface waters in the parts of the Pacific Ocean. By changing the distribution of heat and wind across the Pacific, El Niño alters rainfall patterns for months to seasons. As El Niño becomes more frequent and stronger in the future as a result of climate change, the distribution of mosquito breeding grounds could increase with large rainfalls, resulting in the emergence of new risk areas for Rift Valley fever outbreaks.
In the early months of 2024, an outbreak of RVF was detected in northern Kenya, possibly linked to the ongoing 2023 outbreak in Uganda. 13 human cases were reported and Kenya has implemented a mass animal vaccination program in the affected counties in an attempt to control the outbreak. Both Kenya and Uganda will include clinical trial sites for the vaccine development projects included within this grant.
In recognition of its epidemic potential, Rift Valley fever is listed alongside the likes of Ebola, MERS, Lassa and Nipah, on the WHO’s R+D Blueprint, as well as by the World Organization for Animal Health (WOAH).
Despite first being identified in the 1930s, the disease is vastly under-researched, with no vaccines or other treatments currently available for human use. Under this project and building on earlier work including a Phase I trial of a vaccine candidate, CEPI is working with applicants to advance the development of vaccines against RVF with a focus on endemic regions and underpinned by the principle of equitable access. The project has the following objectives:
1) Phase l/ll clinical testing of the most advanced RVFV candidates, including identification of correlates of protection and their validation, which can facilitate future regulatory approval.
2) Identify potential pathways to licensure either through a pivotal clinical trial or via a preclinical route. If a clinical pathway is chosen, we believe that artificial intelligence may need to be employed to make this viable.
3) Produce clinical trial material suitable for the conduct of Phase I/II trials. It is expected that potential applicants will have already developed a manufacturing process. Plans for scale up for stockpiling after Phase IIb or for a future pivotal Phase III trial should also be included.
4) Develop human vaccines for RVFV which could be used to exemplify and develop a viable One Health approach.
5) Identify supporting technologies and/or innovations which could be useful in the development of other vaccines against the WHO R&D Blueprint pathogens.
Rift Valley fever happens pretty regularly in relatively small numbers, in Africa – and cases have also been reported in the Arabian peninsula. However, occasionally, there are large and very explosive outbreaks that have very large cases and numbers - the disease is estimated to have cost the region $300 million since RVF was first discovered, causing collapses in livestock markets which, at the time, made up the majority of national income for countries like Somalia.
Outbreaks usually start after rainy season, where we get mosquito blooms. The infected mosquitoes then bite animals and the animals bite humans, so we get a spread. At this time, we do not know where the reservoir of disease is, although it is most likely in wild animals. Since its first identification, outbreaks of Rift Valley fever have typically occurred in 4-15-year cycles and have been consistently linked with periods of surges in rainfall that occur as a result of the El Niño phenomenon. This is a climate pattern that describes the unusual warming of surface waters in the parts of the Pacific Ocean. By changing the distribution of heat and wind across the Pacific, El Niño alters rainfall patterns for months to seasons. As El Niño becomes more frequent and stronger in the future as a result of climate change, the distribution of mosquito breeding grounds could increase with large rainfalls, resulting in the emergence of new risk areas for Rift Valley fever outbreaks.
In the early months of 2024, an outbreak of RVF was detected in northern Kenya, possibly linked to the ongoing 2023 outbreak in Uganda. 13 human cases were reported and Kenya has implemented a mass animal vaccination program in the affected counties in an attempt to control the outbreak. Both Kenya and Uganda will include clinical trial sites for the vaccine development projects included within this grant.
In recognition of its epidemic potential, Rift Valley fever is listed alongside the likes of Ebola, MERS, Lassa and Nipah, on the WHO’s R+D Blueprint, as well as by the World Organization for Animal Health (WOAH).
Despite first being identified in the 1930s, the disease is vastly under-researched, with no vaccines or other treatments currently available for human use. Under this project and building on earlier work including a Phase I trial of a vaccine candidate, CEPI is working with applicants to advance the development of vaccines against RVF with a focus on endemic regions and underpinned by the principle of equitable access. The project has the following objectives:
1) Phase l/ll clinical testing of the most advanced RVFV candidates, including identification of correlates of protection and their validation, which can facilitate future regulatory approval.
2) Identify potential pathways to licensure either through a pivotal clinical trial or via a preclinical route. If a clinical pathway is chosen, we believe that artificial intelligence may need to be employed to make this viable.
3) Produce clinical trial material suitable for the conduct of Phase I/II trials. It is expected that potential applicants will have already developed a manufacturing process. Plans for scale up for stockpiling after Phase IIb or for a future pivotal Phase III trial should also be included.
4) Develop human vaccines for RVFV which could be used to exemplify and develop a viable One Health approach.
5) Identify supporting technologies and/or innovations which could be useful in the development of other vaccines against the WHO R&D Blueprint pathogens.
Stichting Wageningen Research RVF Project contract with CEPI was executed in July 2023, with the first three months focussing on consortium agreement negotiations and signatures. The first Joint Management Advisory Group meeting (kick-off meeting) was held in November and Regulatory, Pre-clincial, Correlates of protection and Epidemiology work packages commenced. The CMC Tech transfer of LARISSA II seed material, analytical test procedures and iCELLis bioreactor-based development results has been completed.
University of California, Davis contract with CEPI was executed on 25th August 2023, with the initial priority being sub-contracts with partners to be executed. For the clinical trial, site selection for Phase I has been completed, with sites in the Bagamoyo District in Tanzania selected, utilizing partner Ifakara Health Insitutes (IHI) clinical trial centre based in Bagamoyo town and nearby clinic. Production of the Phase I/II clinical trial material to GMP standards is progressing well and remains on target with timelines. Associated assay development activities continue according to plan, with reagent generation, assay optimization and Protocol Development all ongoing within this reporting period. Epidemiology Study Protocol was successfully submitted to IHI and the Tanzania National Institute of Medical Research (NIMR) IRBs, with approval expected in February and the study due to be initiated in Q2 2024.
University of California, Davis contract with CEPI was executed on 25th August 2023, with the initial priority being sub-contracts with partners to be executed. For the clinical trial, site selection for Phase I has been completed, with sites in the Bagamoyo District in Tanzania selected, utilizing partner Ifakara Health Insitutes (IHI) clinical trial centre based in Bagamoyo town and nearby clinic. Production of the Phase I/II clinical trial material to GMP standards is progressing well and remains on target with timelines. Associated assay development activities continue according to plan, with reagent generation, assay optimization and Protocol Development all ongoing within this reporting period. Epidemiology Study Protocol was successfully submitted to IHI and the Tanzania National Institute of Medical Research (NIMR) IRBs, with approval expected in February and the study due to be initiated in Q2 2024.
To be updated in next reporting period