Advancing Malaria Vaccine Development

ANTIBODY FUNCTIONALITY AGAINST THE MALARIA VACCINE TARGET PLASMODIUM FALCIPARUM

Malaria is a life-threatening disease mostly spread by mosquitoes in tropical countries. In 2021, there were approximately 247 million cases of malaria worldwide with an estimated 619,000 deaths. Plasmodium falciparum is the deadliest malaria-causing parasite and is prevalent throughout Africa, necessitating the development of effective antimalarial vaccines.¹ However, for years scientists struggled to develop a vaccine with sufficient clinical efficacy, as human antibody responses were not of sufficient magnitude or endurance.² 

Thus, an important aspect of the malaria vaccine development project was the characterization of human antibodies that can elicit an effective response and confer functional immunity. One such study published in 2019 by researchers with the University of Oxford investigated the functionality of human monoclonal antibodies against the P. falciparum reticulocyte-binding protein homolog 5 (PfRH5), which is a critical malaria vaccine target due to its role in binding host red blood cells during infection.³ The University of Oxford group first recovered peripheral blood B cells from vaccine recipients in the first clinical trial of a PfRH5-based vaccine, and subsequently isolated a panel of antibodies against PfRH5. 

In this study, Zymo Research’s Mix & Go! DH5 Alpha Competent Cells were used for cloning antibody variable genes prior to transfection. After subsequent protein expression and functional studies, the researchers were able to identify four unique classes of antibodies against PfRH5: neutralizing antibodies, inert antibodies, antagonistic antibodies, and non-neutralizing synergistic antibodies.⁴ This thorough characterization of antibody function and the unexpected discovery of non-neutralizing antibodies that can still work against malaria infection by potentiating the effects of neutralizing antibodies provided a foundation for structure-guided PfRH5-based antimalarial vaccine development. 

Today, there are two malaria vaccines that target P. falciparum recommended by the World Health Organization, which will be distributed to at least 28 countries in Africa.⁴ The vaccines are expected to substantially reduce malaria-related hospitalizations and deaths in vulnerable regions. While the journey to malaria vaccine development and roll-out was a challenging one, important biotechnical tools such as Zymo Research’s Mix & Go! Competent Cells enabled scientists to overcome these hurdles for the greater good of humanity. 

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References

1. Malaria. World Health Organization (2023). https://www.who.int/news-room/fact-sheets/detail/malaria.
2. Draper, S. J., Sack, B. K., King, C. R., Nielsen, C. M., Rayner, J. C., Higgins, M. K., Long, C. A., and Seder, R. A. (2018). Malaria vaccines: recent advances and new horizons. Cell Host & Microbe, 24(1), 43–56. https://doi.org/10.1016/j.chom.2018.06.008.
3. Alanine, D. G. W., Quinkert, D., Kumarasingha, R., Mehmood, S., Donnellan, F. R., Minkah, N. K., Dadonaite, B., Diouf, A., Galaway, F., Silk, S. E., Jamwal, A., Marshall, J. M., Miura, K., Foquet, L., Elias, S. C., Labbé, G. M., Douglas, A. D., Jin, J., Payne, R. O., Illingworth, J. J., Pattinson, D. J., Pulido, D., Williams, B. G., de Jongh, W. A., Wright, G. J., Kappe, S. H. I., Robinson, C. V., Long, C. A., Brabb, B. S., Gilson, P. R., Higgins, M. K., and Draper, S. J. (2019). Human Antibodies that Slow Erythrocyte Invasion Potentiate Malaria-Neutralizing Antibodies. Cell, 178(1), 216–228.e21. https://doi.org/10.1016/j.cell.2019.05.025.
4. WHO recommends R21/Matrix-M vaccine for malaria prevention in updated advice on immunization. World Health Organization (2023). https://www.who.int/news/item/02-10-2023-who-recommends-r21-matrix-m-vaccine-for-malaria-prevention-in-updated-advice-on-immunization.