Can monoclonal antibodies effectively treat malaria? Scientists say the answer is a resounding ‘yes’

Monoclonal antibodies provide protection against a wide range of infectious microbes, and now, in a series of elegant laboratory experiments, scientists have uncovered how a pair of these lab-engineered molecules fight malaria.

The newly developed antibodies have arrived at a critical time. Gains against mosquitoes in the years-long ground offensive have largely stalled; the war against the disease itself has slowed.

In many regions of the world, malaria treatments and mosquito-control efforts are beset by drug and insecticide resistance. Even the widely touted anti-malaria vaccination campaigns aimed at children have yet to immunize a sufficient number to outpace the mosquito-driven scourge.

An interdisciplinary team of U.S. researchers from the embattled Vaccine Research Center in Bethesda, Maryland, developed the two monoclonal antibodies, also known simply as mAbs. These antibodies bind to distinct regions on the surface of an early-developmental stage of the deadliest malaria parasite on the planet, Plasmodium falciparum. Details of the research are published in Science Translational Medicine.

The Vaccine Research Center is a division of the National Institute of Allergy and Infectious Diseases whose future now hangs in the balance amid cutbacks. The collaborative group of scientists has since disbanded, moving on to other labs in the U.S. and elsewhere in the world, according to information in the journal.

The analysis, nevertheless, is a deep dive into how the two mAbs, CIS43LS and L9LS, bind to surface proteins and deactivate the malaria parasite. The research provides evidence that mAbs can be extraordinarily effective in the treatment of malaria.

“Malaria is a big public health issue worldwide, and especially in African countries,” Dr. Neville K. Kisalu, lead author of the study, told Medical Xpress. He has long advocated for expanding the armamentarium for malaria because of the overwhelming number of cases, especially severe ones that lead to death. The World Health Organization estimates the annual number of malaria cases at 263 million.

In the study, Kisalu and colleagues estimated that malaria “causes approximately 700,000 deaths globally, primarily affecting children in sub-Saharan Africa.” That number differs substantially from data collected by WHO, which estimates 597,000 annual deaths. Kisalu attributes the difference to methods of assessment.

The mAb research was conducted in two murine models in a study designed to ferret out the targets that the two mAbs zero in on. Clinical trials have already shown that mAbs have several advantages: they’re life-sparing, offer rapid protection after a single dose, and are safe to use.

Researchers revealed that mAbs bind to the circumsporozoite protein, which stipples the surface of the parasite’s sporozoite stage of development, which occurs early in the malaria parasite’s life cycle in human hosts. There are about 19 different developmental stages that the parasites undergo, first in mosquitoes, and then in humans. Monoclonal antibodies prevent the parasite from entering the liver and transforming into a more life-threatening stage, said Kisalu, an immunologist.

Both antibodies, CIS43LS and L9LS, protected against malaria in the mouse models in a manner that didn’t require Fc binding to Fc receptors on the parasite.

Picture an antibody as shaped like the letter Y. The Fc region (fragment crystallizable) is the long tail portion. The mAbs targeted several regions instead. Findings from the research could inform the development of the next generation of monoclonal antibody therapies for the disease.

“Human monoclonal antibodies, CIS43LS and L9LS, show high-affinity binding, targeting distinct regions on the Plasmodium falciparum circumsporozoite protein—PfCSP—and are highly effective in preventing malaria in humans,” Kisalu said.

Developing mAbs for malaria makes sense, he said, because antibodies have been engineered to successfully treat other types of infectious diseases. COVID-19 is an example of a virus that succumbs to monoclonal antibody therapy.

“Antibodies mediate protection against a wide range of pathogens through binding and neutralizing the pathogen,” Kisalu and colleagues wrote in Science Translational Medicine. The team noted that the two malaria mAbs are based on human antibodies that demonstrated extraordinary capabilities to neutralize malaria parasites.

Although vaccination and other public health initiatives, such as vector control, have had a notable effect on lowering malaria cases worldwide, the gains of the past several years have plateaued and there are now increases in cases across multiple geographic areas.

What is needed to address the surge, Kisalu said, is a broad range of interventions and monoclonal antibodies are an important addition. Unlike the recently approved vaccines, mAbs can be administered to people of all ages.

In regions where malaria is endemic, human adults tend to harbor active malaria parasites in their blood, Kisalu explained, adding that these parasites can be picked up by female Anopheles mosquitoes during a bloodmeal. These active parasites can then be passed to others, especially vulnerable children, in subsequent bites.

“Adults are the reservoir; they’re harboring it,” Kisalu said, referring to malaria parasites. “When they are in the blood, they are there in the billions. But that’s a nice window of opportunity to target the parasites before they reach the liver.”

The hope is to make anti-malaria mAbs more efficient by engineering them to bind more effectively to their targets. Increasing the binding affinity of next-generation mAbs may further increase their potency by about two-to-threefold, a move that could also help reduce costs, Kisalu and his colleagues conclude.

© 2025 Science X Network

Monoclonal antibodies provide protection against a wide range of infectious microbes, and now, in a series of elegant laboratory experiments, scientists have uncovered how a pair of these lab-engineered molecules fight malaria.

The newly developed antibodies have arrived at a critical time. Gains against mosquitoes in the years-long ground offensive have largely stalled; the war against the disease itself has slowed.

In many regions of the world, malaria treatments and mosquito-control efforts are beset by drug and insecticide resistance. Even the widely touted anti-malaria vaccination campaigns aimed at children have yet to immunize a sufficient number to outpace the mosquito-driven scourge.

An interdisciplinary team of U.S. researchers from the embattled Vaccine Research Center in Bethesda, Maryland, developed the two monoclonal antibodies, also known simply as mAbs. These antibodies bind to distinct regions on the surface of an early-developmental stage of the deadliest malaria parasite on the planet, Plasmodium falciparum. Details of the research are published in Science Translational Medicine.

The Vaccine Research Center is a division of the National Institute of Allergy and Infectious Diseases whose future now hangs in the balance amid cutbacks. The collaborative group of scientists has since disbanded, moving on to other labs in the U.S. and elsewhere in the world, according to information in the journal.

The analysis, nevertheless, is a deep dive into how the two mAbs, CIS43LS and L9LS, bind to surface proteins and deactivate the malaria parasite. The research provides evidence that mAbs can be extraordinarily effective in the treatment of malaria.

“Malaria is a big public health issue worldwide, and especially in African countries,” Dr. Neville K. Kisalu, lead author of the study, told Medical Xpress. He has long advocated for expanding the armamentarium for malaria because of the overwhelming number of cases, especially severe ones that lead to death. The World Health Organization estimates the annual number of malaria cases at 263 million.

In the study, Kisalu and colleagues estimated that malaria “causes approximately 700,000 deaths globally, primarily affecting children in sub-Saharan Africa.” That number differs substantially from data collected by WHO, which estimates 597,000 annual deaths. Kisalu attributes the difference to methods of assessment.

The mAb research was conducted in two murine models in a study designed to ferret out the targets that the two mAbs zero in on. Clinical trials have already shown that mAbs have several advantages: they’re life-sparing, offer rapid protection after a single dose, and are safe to use.

Researchers revealed that mAbs bind to the circumsporozoite protein, which stipples the surface of the parasite’s sporozoite stage of development, which occurs early in the malaria parasite’s life cycle in human hosts. There are about 19 different developmental stages that the parasites undergo, first in mosquitoes, and then in humans. Monoclonal antibodies prevent the parasite from entering the liver and transforming into a more life-threatening stage, said Kisalu, an immunologist.

Both antibodies, CIS43LS and L9LS, protected against malaria in the mouse models in a manner that didn’t require Fc binding to Fc receptors on the parasite.

Picture an antibody as shaped like the letter Y. The Fc region (fragment crystallizable) is the long tail portion. The mAbs targeted several regions instead. Findings from the research could inform the development of the next generation of monoclonal antibody therapies for the disease.

“Human monoclonal antibodies, CIS43LS and L9LS, show high-affinity binding, targeting distinct regions on the Plasmodium falciparum circumsporozoite protein—PfCSP—and are highly effective in preventing malaria in humans,” Kisalu said.

Developing mAbs for malaria makes sense, he said, because antibodies have been engineered to successfully treat other types of infectious diseases. COVID-19 is an example of a virus that succumbs to monoclonal antibody therapy.

“Antibodies mediate protection against a wide range of pathogens through binding and neutralizing the pathogen,” Kisalu and colleagues wrote in Science Translational Medicine. The team noted that the two malaria mAbs are based on human antibodies that demonstrated extraordinary capabilities to neutralize malaria parasites.

Although vaccination and other public health initiatives, such as vector control, have had a notable effect on lowering malaria cases worldwide, the gains of the past several years have plateaued and there are now increases in cases across multiple geographic areas.

What is needed to address the surge, Kisalu said, is a broad range of interventions and monoclonal antibodies are an important addition. Unlike the recently approved vaccines, mAbs can be administered to people of all ages.

In regions where malaria is endemic, human adults tend to harbor active malaria parasites in their blood, Kisalu explained, adding that these parasites can be picked up by female Anopheles mosquitoes during a bloodmeal. These active parasites can then be passed to others, especially vulnerable children, in subsequent bites.

“Adults are the reservoir; they’re harboring it,” Kisalu said, referring to malaria parasites. “When they are in the blood, they are there in the billions. But that’s a nice window of opportunity to target the parasites before they reach the liver.”

The hope is to make anti-malaria mAbs more efficient by engineering them to bind more effectively to their targets. Increasing the binding affinity of next-generation mAbs may further increase their potency by about two-to-threefold, a move that could also help reduce costs, Kisalu and his colleagues conclude.

© 2025 Science X Network