Now is the time to accelerate the development of second-generation malaria vaccines through investment, innovation and public-private partnerships.

At the World Vaccine Congress 2024, an EVI-organised panel discussion explored the lessons learnt from licensed malaria vaccines, current strategies for developing the next-generation malaria vaccines, and the opportunities that novel technologies and public-private partnerships create for accelerating novel malaria vaccines.

December 18, 2024

Malaria predominantly affects the rural poor in low-income countries and kills mostly young children. According to the World Malaria Report 2024  released by the WHO a week ago. An estimated 597,000 malaria deaths occurred in 2023 with a mortality rate of 13.7 per 100 000, a steady decrease from 622 000 and 14.9 deaths per 100 000, respectively, in 2020. The estimated number of malaria cases in 2023 was 263 million, with an incidence of 60.4 cases per 1000 population at risk. This is an increase of 11 million cases from the previous year and a rise in incidence from 58.6 cases per 1000 population at risk in 2022. There is also evidence indicating artemisinin drug resistance in the WHO African region. The report shows that the job of controlling malaria is far from done.

Currently, two licensed malaria vaccines, MosquirixTM and R21/Matrix-MTM, have been added to the arsenal of tools for malaria control. As of early December 2024, the WHO reports that 17 countries have introduced these malaria vaccines into routine childhood immunisation programs, with additional nations  planning to follow suit next year  with support from Gavi, the Vaccine Alliance, and WHO. The full impact of these vaccines on malaria mortality and morbidity will only be realised in coming years as their introduction and coverage expand in areas with high to moderate malaria transmission. These first-generation malaria vaccines represent a ground breaking milestone as the only licensed vaccines against any parasitic disease. However, limitations in their efficacy and durability of protection highlight the need for second-generation malaria vaccines. At EVI, alongside our partners in the multi-stage malaria vaccine consortium (MMVC), UltiMalVax and CAPTIVATE consortia, we remain committed to advancing the development of these next-generation malaria vaccines.   

Recently, a panel discussion at the World Vaccine Congress 2024 explored the lessons learnt from licensed malaria vaccines to inform strategies for developing next-generation malaria vaccines. The panel brought together industry leaders in malaria vaccine development Dr. Katie Ewer (senior project leader, malaria vaccines, GSK Vaccines) and Dr. Thierry Rolling (director, clinical development, BioNTech); MMVC and UltiMalVax consortia work package leader Prof. Sumi Biswas (group leader, transmission-blocking malaria vaccine, University of Oxford & co- founder & CSO, SpyBiotech); CAPTIVATE consortium scientific lead, Prof. Meta Roestenberg (clinical head, controlled human infection center, Leiden University) and EVI’s Malaria programme manager, Dr Irene Nailain Nkumama as the moderator.

Some of the key lessons from first-generation vaccines highlighted by the panellists include: the potential for dose sparing and increased immunogenicity by optimising vaccine regimens in early clinical trials; the importance of targeting multiple stages of the parasite (blood-stage, liver-stage and transmission-blocking antigens) to increase vaccine efficacy/effectiveness; the value of early collaboration with large manufacturers to ensure the vaccines are affordable and scalable; and the need for vaccines targeting P. vivax to achieve global malaria elimination and prevent species replacement. The discussion also explored the opportunities presented by novel technologies, such as mRNA-LNP platforms, which can be more efficient in developing multi-antigen vaccines, and T-cell sequencing to identify liver-stage antigens that mediate immunity.

Public-private partnerships were highlighted as essential accelerators in malaria vaccine development, as exemplified by the collaboration between the University of Oxford, Novavax AB and the Serum Institute of India in developing the R21/Matrix-MTM vaccine.

However, unique challenges remain for second-generation malaria vaccines, especially multi-stage vaccines. These include balancing affordability and efficacy when exploring new technologies, such as mRNA, or multi-antigen formulations. A desirable second-generation malaria vaccine should have higher efficacy while remaining affordable for low-income countries and GAVI markets.

Panellists also emphasised the need for a clear regulatory framework aligning next-generation vaccines with GAVI and WHO regulatory expectations, particularly for multi-stage vaccines. Including providing guidance on how to accelerate clinical development e.g. whether efficacy must be demonstrated for each vaccine component individually before inclusion in a multi-component vaccine. The lack of validated immunological correlates of protections for immune-bridging was also identified as an urgent gap.

The panellists concluded that while progress has been made, much work lies ahead. Accelerating the development of second-generation malaria vaccines will require investment, innovation and strengthened public-private partnerships.

Learn more about EVI-associated second-generation malaria vaccine consortia:

Multi-stage malaria vaccine consortium (MMVC).

This project is part of the EDCTP2 programme (grant number RIA2016V-1649-MMVC) supported by the European Union.

A vaccine for malaria eradication (UltiMalVax).

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or the European Health and Digital Executive Agency. Neither the European Union nor the granting authority can be held responsible for them. Grant agreement No 101080928.

Correlates of protective immunity-driven investigation of malaria vaccine combination strategies (CAPTIVATE).

Funded by the European Union. Views and opinions expressed are however those of the author(s) only and do not necessarily reflect those of the European Union or European Health and Digital Executive Agency (HADEA). Neither the European Union nor the granting authority can be held responsible for them. Grant agreement No 101081028.