Periodic Reporting for period 1 - UltiMalVax (A Vaccine Targeting Eradication of Malaria)
Reporting period: 2023-05-01 to 2024-10-31
There were about 597,000 malaria deaths globally in 2023 as estimated by WHO with the great majority of these in Africa, and mostly in children. Malaria is a particularly unfair driver of greater human inequity, predominantly affecting not just many of the lowest income countries in the world, but within these the rural poor, and amongst these killing mostly young children. On top of this mortality burden, there were over 263 million clinical cases of malaria in 2023. This impact of malaria occurs despite over $4 billion dollars now being spent annually on malaria control. Insecticide and drug resistance as well as the effects of COVID-19 pandemic have contributed to the stalling of malaria control and elimination progress. New tools are needed to address this unacceptable disease burden with vaccines as the most attractive short to medium-term solution. Following tremendous collaborative research efforts, there are now two WHO pre-qualified malaria vaccines, RTS,S/AS01 (MosquirixTM) and R21/Matrix-M, which are anticipated to greatly accelerate malaria control efforts following introductions in high to moderate malaria transmission settings.
The UltiMalVax consortium, with complementary support from other funders, builds on the recent achievements of MosquirixTM and R21/Matrix-M vaccines and lessons from the COVID-19 pandemic to design what could be the “ultimate” vaccine needed for malaria elimination and eradication. In this ambitious, accelerated, research programme the consortium will develop the first vaccine with clinical efficacy in preventing both P. falciparum and P. vivax malaria, which would also impact the transmission of both parasites with a single vaccine formulation.
The UltiMalVax consortium, with complementary support from other funders, builds on the recent achievements of MosquirixTM and R21/Matrix-M vaccines and lessons from the COVID-19 pandemic to design what could be the “ultimate” vaccine needed for malaria elimination and eradication. In this ambitious, accelerated, research programme the consortium will develop the first vaccine with clinical efficacy in preventing both P. falciparum and P. vivax malaria, which would also impact the transmission of both parasites with a single vaccine formulation.
To achieve its goal, the consortium generated and assessed virus-like particle (VLP) vaccines in potent saponin adjuvants sporozoite and transmission-blocking parasite antigens. This includes adopting new VLP design technologies, e.g. SpyCatcher bonding, that allow bivalent antigen display. In addition to protecting against both parasite species, the P. falciparum and P. vivax anti-sporozoite antigens will also contribute to a marked reduction in malaria transmission. The VLP-adjuvant formulations were assessed for immunogenicity and efficacy in animal models.
In addition, new thermostable mRNA-LNP vaccines expressing sporozoite or transmission-blocking parasite antigens were generated and assessed for immunogenicity and efficacy in animal models. Moreover, the consortium identified, manufactured and characterised novel adjuvant components. A lead vaccine candidate will be down-selected based on pre-clinical efficacy and induction of functional transmission-blocking antibodies, before GMP manufacture and a clinical trial in year 4.
In addition, new thermostable mRNA-LNP vaccines expressing sporozoite or transmission-blocking parasite antigens were generated and assessed for immunogenicity and efficacy in animal models. Moreover, the consortium identified, manufactured and characterised novel adjuvant components. A lead vaccine candidate will be down-selected based on pre-clinical efficacy and induction of functional transmission-blocking antibodies, before GMP manufacture and a clinical trial in year 4.
The consortium has generated multiple immunogens that entail the use of different VLP technologies and various mRNA-LNP designs and formulations. The consortium also explored different ways of incorporating multiple antigens into a single immunogen. Ongoing animal experiments with the generated immunogens will reveal the leading candidates for further development to create a high-efficacy multi-species vaccine for malaria eradication.
The data from these experiments also have potential scientific impact as it is likely to be of value to the scientific community in informing the advantages and disadvantages of each explored approach thereby influencing the development of vaccines against other pathogens. In addition, the consortium has developed and characterised new adjuvant components which can be utilised in vaccines against other pathogens.
The economic and societal impact of the project will be realised once the consortium achieves its goal of creating the ultimate multi-stage multi-species highly effective malaria vaccine, and the vaccine is implemented widely.
The data from these experiments also have potential scientific impact as it is likely to be of value to the scientific community in informing the advantages and disadvantages of each explored approach thereby influencing the development of vaccines against other pathogens. In addition, the consortium has developed and characterised new adjuvant components which can be utilised in vaccines against other pathogens.
The economic and societal impact of the project will be realised once the consortium achieves its goal of creating the ultimate multi-stage multi-species highly effective malaria vaccine, and the vaccine is implemented widely.