Malaria
Malaria
Introduction
Malaria is a preventable and treatable disease with effective solutions, yet in 2023 alone, there were an estimated 263 million cases worldwide, and approximately 597,000 deaths. The African Region bears the heaviest burden of malaria, accounting for an estimated 94% of global cases and 95% of malaria-related deaths in 2023. Historically, cuts to global health funding or malaria control programs have led to a resurgence of disease, calling for the Gates Foundation to challenge the global community to strive for malaria eradication as the only sustainable approach to addressing malaria.
The biology of Malaria
Malaria is an acute febrile illness caused by Plasmodium parasites, typically transmitted by Anopheles mosquitoes. The species P. falciparum is the deadliest malaria parasite and the most prevalent in Africa, while P. vivax is the dominant malaria parasite in most countries outside Sub-Saharan Africa.
Malaria symptoms include chills, fever, and headaches, that typically appear between 10 to 15 days after a person is bitten by an infected mosquito. Though identifying these symptoms as malaria can be difficult, if left untreated, P. falciparum malaria can progress to severe illness and death within a period of 24 hours. Children younger than five years, non-immune adults and pregnant women, and patients with HIV/AIDS are most at risk of developing severe illness after contracting malaria.
Monthly preventative chemotherapy and new vaccines are helping to reduce the burden of malaria in vulnerable populations. For example, the World Health Organization in 2023 recommended that children in regions with moderate-to-high P. falciparum malaria transmission be given the RTS,S/AS01 (MosquirixTM) or R21/Matrix-M malaria vaccine in a schedule of 4 doses from five months of age to reduce malaria disease burden. Yet, gaps in vaccine coverage, challenges in delivery and adherence, as well an emerging drug resistance, mean that more potent and easier to deliver malaria prevention solutions are needed.
Due to the limitations of existing solutions and the impact malaria has on children in LMICs, Gates MRI has initiated the development of a monoclonal antibody (mAb) with the goal of preventing P. falciparum malaria infections in infant and pediatric populations.
Approach
Stemming from a collaboration with the biotechnology company, Atreca, Inc., Gates MRI is developing a candidate prophylactic mAb that may potentially provide prolonged protection against malaria infection. With a single injection, the goal of the program is to prevent malaria infection and illness caused by the P. falciparum parasite for at least four months in children 3 months to 5 years of age in endemic countries, and any countries with active falciparum malaria outbreaks. The mAb candidate – an engineered version of a human antibody isolated from a RTS,S/AS01 vaccine trial participant – has demonstrated the ability to elicit protection against malaria infection in mice across multiple studies by targeting the P. falciparum circumsporozoite protein (CSP). Gates MRI’s mAb program is currently in Phase 1 of development, including a clinical trial currently underway in Uganda (ClinicalTrials.gov ID NCT06408857).
To further support the efforts towards elimination, Gates MRI is completing the preclinical development of MAV02, a novel vaccine combining an engineered nanoparticle (FtNP-203) expressing portions of the P. falciparum CSP, combined with a novel adjuvant. Both vaccine components were the result of long-term discovery grant investments by the Gates Foundation, with Gates MRI carrying responsibility for developing large scale manufacturing methods and preclinical toxicology.
