A team of researchers from the National Institutes of Health (NIH) found a new class of antibodies that target a previously unknown component of the malaria parasite. Their findings, reported in Science, show that these antibodies could lead to more effective malaria prevention approaches. Animal experiments demonstrated the potency of the newly discovered antibody, MAD21-101, to protect against malaria. According to the researchers, this discovery is significant because it targets areas of the parasite that conventional malaria vaccines do not, providing a novel way to combat a disease that affects millions of people globally. 

Plasmodium parasites, which enter the body through the bites of infected mosquitos, cause malaria. Malaria is rare in the United States, but it remains a major worldwide health concern, particularly in sub-Saharan Africa. The World Health Organisation (WHO) estimates that there will be 263 million malaria cases in 2023, resulting in 597,000 deaths. Plasmodium falciparum is the most lethal of the five Plasmodium species that cause malaria, especially in African countries where young children are most at risk of dying from the disease. Developing novel, safe, and effective malaria prevention measures is vital to decreasing the severe impact on public health.

Several new malaria-fighting techniques have emerged in recent years, including vaccines tailored specifically for young children in high-risk areas. Another intriguing option is to use monoclonal antibodies (mAbs), which are laboratory-made proteins that bind to and neutralise specific targets in the body. Clinical investigations in malaria-endemic areas have demonstrated that these anti-malarial antibodies are both safe and effective. Most of these antibodies attack the parasite as a sporozoite in the mosquito, just before it enters the bloodstream. Once inside the liver, the sporozoite matures into blood-stage parasites that infect red blood cells and cause sickness. These mAbs serve to limit disease progression by inhibiting the sporozoite before it infects the liver. 

So far, the best mAbs that fight malaria have been able to target a protein on the surface of the sporozoite. This protein is called the circumsporozoite protein (PfCSP). Both malaria vaccines target the same protein in the central repeat region. However, the researchers in this new study aimed to uncover antibodies that would attach to distinct sections of the parasite that are not currently targeted by vaccines or mAbs. 

The research team, led by scientists from the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health (NIH), used a novel technique to look for alternative binding sites on the sporozoite, known as epitopes. They sought human antibodies produced in response to exposure to the entire sporozoite, not just specific parts. After testing various antibodies in a mouse model, scientists determined that MAD21-101 was the most effective at providing protection. 

It binds to pGlu-CSP, a special part of PfCSP that is not in the core repeat region. This epitope is particularly intriguing because it is consistent across different strains of Plasmodium falciparum. Furthermore, it is exposed only after a specific growth stage of the sporozoite but remains extensively accessible, making it an excellent target for the immune system. Current vaccines do not include pGlu-CSP, so taking the novel antibodies concurrently would not interfere with existing immunisations. This opens the possibility of employing these antibodies to protect neonates and other vulnerable groups who have not yet received a vaccine but may benefit from both the antibody and the vaccine in the future. 

According to the researchers, these findings could help influence the development of next-generation malaria vaccines and antibodies. They hope that their technique could aid in the development of novel medicines for other infectious diseases caused by similar organisms. Despite the intriguing findings, further research is necessary to fully comprehend the functioning of these novel antibodies and guarantee their safety and effectiveness in humans. 

The development of this novel antibody class is a promising step towards better malaria prevention. If additional research confirms its efficacy, it could provide a strong new weapon for reducing malaria transmission and saving lives in areas most impacted by the fatal disease.