A recent study conducted by researchers at the National Institutes of Health (NIH) has identified a novel class of antibodies that target a previously unexplored region of the malaria parasite. These antibodies have shown promising results in protecting against malaria parasites in animal models. This discovery opens up new possibilities for preventing malaria, as these antibodies bind to regions of the parasite that are not currently targeted by existing malaria vaccines. Malaria is a life-threatening disease caused by Plasmodium parasites, transmitted through the bites of infected mosquitoes, with devastating global impact.
Plasmodium falciparum is the most common species of malaria in African countries, where young children account for the majority of malaria deaths. Safe and effective countermeasures are essential for reducing the burden of malaria, with the World Health Organization estimating 263 million cases and 597,000 deaths in 2023. While vaccines are being rolled out for young children in malaria-endemic regions, anti-malarial monoclonal antibodies (mAbs) have emerged as a promising new tool in the fight against malaria. These antibodies have shown efficacy in preventing P. falciparum infection in adults and children in early clinical trials.
Existing anti-malarial mAbs target the sporozoite stage of the parasite, preventing it from infecting the liver and progressing to the blood stage of the disease. However, the most effective mAbs identified so far bind to a protein on the sporozoite surface called PfCSP, specifically in the central repeat region also targeted by current malaria vaccines. The researchers in the NIH study sought to identify new mAbs that target different sites on the sporozoite surface, using a novel approach. By isolating human mAbs produced in response to whole sporozoites, they identified a potent mAb named MAD21-101 that demonstrated protection against P. falciparum infection in mice.
The new mAb, MAD21-101, binds to an epitope on PfCSP known as pGlu-CSP, which is conserved across different strains of P. falciparum. This epitope is exposed on the sporozoite surface after a specific developmental step, making it a potentially effective target for triggering an immune response in a vaccine. Since pGlu-CSP is not included in current malaria vaccines, mAbs targeting this epitope are unlikely to interfere with vaccine efficacy. This presents an opportunity to use this new class of antibodies to prevent malaria in at-risk populations who have not yet received a vaccine but may do so in the future.
The findings from this study have significant implications for malaria prevention strategies and could lead to the development of new antibodies and vaccines against the disease. Further research is needed to explore the activity and effectiveness of this newly identified antibody class and epitope. The approach used in this study may also have broader applications for developing countermeasures against other pathogens, not limited to malaria. Overall, this research represents a promising step forward in the fight against malaria and other infectious diseases.
