New monoclonal antibody prevents malaria infection in early clinical trial

Malaria remains one of the leading causes of death among children in sub-Saharan Africa, claiming more than 600,000 lives each year worldwide with limited efficacy in currently available treatments and vaccines. Now a new early-stage clinical trial found that a novel monoclonal antibody provided dose-dependent full protection against the malaria parasite with minimal side effects.

Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) conducted the trial in healthy volunteers who were exposed, in a controlled manner, to bites, from mosquitoes infected with the malaria parasite.

Results were recently published in The Lancet Infectious Diseases. The researchers conducted the trial in collaboration with the Gates Medical Research Institute.

“Despite major advances, malaria continues to devastate families and communities across Africa,” said study lead author Kirsten E. Lyke, MD, Professor of Medicine at UM School of Medicine and principal investigator at CVD. “This new monoclonal antibody could transform how we prevent malaria in young children and pregnant women. Unlike vaccines that may require multiple doses or boosters, a single injection of a long-acting antibody could provide immediate, months-long protection. It’s a fundamentally different way to stop infection before it starts.”

Monoclonal antibodies (mAbs) are laboratory-made protein clones that mimic the body’s natural immune defenses. MAM01 targets a highly conserved region of the Plasmodium falciparum circumsporozoite protein—a protein on the parasite’s outer surface—to block infection before it reaches the bloodstream.

The Phase 1, double-blind, placebo-controlled trial enrolled 38 healthy adults aged 18 to 50 with no prior malaria exposure. Participants received one dose of MAM01 or a placebo, and were then exposed to mosquitoes carrying malaria, several months after dosing. This was done under carefully controlled conditions known as a challenge study. After the malaria challenge, none of the participants who received the highest dose of the monoclonal antibody developed infection, compared to all the participants in the placebo group.

“These early results suggest that this monoclonal antibody can provide reliable protection against malaria, which continues to disproportionately affect children who live in low and middle-income countries,” said study co-author Matthew B. Laurens, MD, MPH, Professor of Pediatrics and Director of the Malaria International Clinical Trials Unit at CVD. “This is an important proof-of-concept for the field and a step forward for health equity.”

No treatment-related serious adverse events occurred.

“The CVD research team is now exploring optimized dosing and cost-reduction strategies to make monoclonal antibody–based prevention feasible in malaria-endemic regions,” said UM School of Medicine Dean Mark T. Gladwin, MD, who is also the Vice President for Medical Affairs at the University of Maryland, Baltimore (UMB), and the John Z. and Akiko K. Bowers Distinguished Professor. “Testing of this preventive treatment has already started in young children in Uganda, based on the promising results from the first trial conducted here.”

Added James Campbell, MD, MS, Interim Director of the Center for Vaccine Development and Global Health: “This study represents real hope for millions of children at risk. CVD has been a global leader in malaria research for more than 50 years, and these findings advance our mission to eliminate this disease through innovative science.”

Malaria remains one of the leading causes of death among children in sub-Saharan Africa, claiming more than 600,000 lives each year worldwide with limited efficacy in currently available treatments and vaccines. Now a new early-stage clinical trial found that a novel monoclonal antibody provided dose-dependent full protection against the malaria parasite with minimal side effects.

Researchers at the University of Maryland School of Medicine’s Center for Vaccine Development and Global Health (CVD) conducted the trial in healthy volunteers who were exposed, in a controlled manner, to bites, from mosquitoes infected with the malaria parasite.

Results were recently published in The Lancet Infectious Diseases. The researchers conducted the trial in collaboration with the Gates Medical Research Institute.

“Despite major advances, malaria continues to devastate families and communities across Africa,” said study lead author Kirsten E. Lyke, MD, Professor of Medicine at UM School of Medicine and principal investigator at CVD. “This new monoclonal antibody could transform how we prevent malaria in young children and pregnant women. Unlike vaccines that may require multiple doses or boosters, a single injection of a long-acting antibody could provide immediate, months-long protection. It’s a fundamentally different way to stop infection before it starts.”

Monoclonal antibodies (mAbs) are laboratory-made protein clones that mimic the body’s natural immune defenses. MAM01 targets a highly conserved region of the Plasmodium falciparum circumsporozoite protein—a protein on the parasite’s outer surface—to block infection before it reaches the bloodstream.

The Phase 1, double-blind, placebo-controlled trial enrolled 38 healthy adults aged 18 to 50 with no prior malaria exposure. Participants received one dose of MAM01 or a placebo, and were then exposed to mosquitoes carrying malaria, several months after dosing. This was done under carefully controlled conditions known as a challenge study. After the malaria challenge, none of the participants who received the highest dose of the monoclonal antibody developed infection, compared to all the participants in the placebo group.

“These early results suggest that this monoclonal antibody can provide reliable protection against malaria, which continues to disproportionately affect children who live in low and middle-income countries,” said study co-author Matthew B. Laurens, MD, MPH, Professor of Pediatrics and Director of the Malaria International Clinical Trials Unit at CVD. “This is an important proof-of-concept for the field and a step forward for health equity.”

No treatment-related serious adverse events occurred.

“The CVD research team is now exploring optimized dosing and cost-reduction strategies to make monoclonal antibody–based prevention feasible in malaria-endemic regions,” said UM School of Medicine Dean Mark T. Gladwin, MD, who is also the Vice President for Medical Affairs at the University of Maryland, Baltimore (UMB), and the John Z. and Akiko K. Bowers Distinguished Professor. “Testing of this preventive treatment has already started in young children in Uganda, based on the promising results from the first trial conducted here.”

Added James Campbell, MD, MS, Interim Director of the Center for Vaccine Development and Global Health: “This study represents real hope for millions of children at risk. CVD has been a global leader in malaria research for more than 50 years, and these findings advance our mission to eliminate this disease through innovative science.”