Monoclonal antibody being developed for malaria to advance this year

Malaria continues to impact low- to middle-income countries in sub-Saharan Africa, India and parts of South Asia. According to the World Health Organization (WHO), malaria kills more than 600,000 people each year, with the most recent figure estimating that 619,000 people succumbed to the disease in 2021.

April 25 marks World Malaria Day, which serves as a reminder to people here in the United States and other places where malaria is not endemic of its health footprint on populations. Malaria was endemic in the United States before a concerted effort was made by spraying and it was declared eliminated in the country in 1951.

In recent weeks, the University of Oxford announced the malaria vaccineR21/Matrix-M, has been approved for use in Ghana (one of the endemic countries.)

The vaccine was a collaborative effort between Oxford, the Kenya Medical Research Institute, the London School of Hygiene & Tropical Medicine, Novavax and the Serum Institute of India.

Another organization working hard on this vector-borne disease is the Bill & Melinda Gates Medical Research Institute. Gates MRI has collaborated with Atreca on the development of MAM01 (Mosquirix), a novel monoclonal antibody (mAb) that could provide prolonged protection against malaria infection. This is what the organization is working on. Specifically, their program aims to develop this prophylactic monoclonal antibody to prevent malaria caused by P sickles for 3 to 6 months (during the rainy season) after administration in children aged 3 years to less than 60 months in areas eligible for seasonal malaria chemoprevention (SMC), endemic countries and all countries with active malaria epidemics.

Scott Miller, MD, Associate Director, Medical Interventions, The Gates Medical Research Institute recently spoke with Contagion and he offered some ideas about the antibody and the foundation’s plans in this area.

Contagion: Although the United States has not seen the problem of malaria for a number of years, with climate change, malaria may eventually return to this country in greater numbers. What should clinicians and the general public know about this?
Miller: Malaria was eliminated in the United States in the 1950s. There are more than 2,000 cases of malaria imported into the United States each year by travelers returning from malaria-endemic areas. Anopheles mosquitoes are still present in many parts of the United States, and local outbreaks have occurred among these returning travelers, but are never sustained due to improved housing. Therefore, the reintroduction of malaria would be highly unlikely despite climate change, unlike the increased risk of dengue fever or other viruses.

Contagion: Regarding the Gates Malaria Program as a whole, can you provide an update on the latest initiatives and news on this?
Miller: The malaria program at Gates MRI is new, it started last year. Our first product development effort is on the monoclonal antibody, but we also plan to work on vaccines for people of all ages to help eliminate malaria.

Contagion: Thinking of THE Gates MRI collaboration with Atreca on the development of MAM01 which may provide protection against malaria infection. Can you give an overview of the therapy and its mechanism of action?
Miller: MAM01 is a long-acting injectable drug for the prevention of falciparum malaria. It is a monoclonal antibody targeting a conserved region of the dominant protein on the surface of the sporozoite, the invasive stage of the parasite inoculated by the mosquito in its saliva.

The antibody has been modified to optimize manufacturability and extend its half-life. Its mechanism of action is to bind the sporozoite in the skin or bloodstream to prevent motility and allow destruction by the human immune system. Further details on its selection and optimization can be found in a new article on a pre-print site.

Contagion: Where is this therapy in terms of clinical trials?
Miller: The phase 1 trial will begin in the second half of this year in the United States and next year in sub-Saharan Africa.