Abstract

Plasmodium falciparum malaria remained a formidable public health challenge in high-transmission regions, 
particularly sub-Saharan Africa. Despite existing control measures, malaria continues to cause significant morbidity 
and mortality, underlining the urgent need for novel prevention strategies. Monoclonal antibodies (mAbs) have 
emerged as promising prophylactic agents due to their targeted specificity and potential for durable protection. This 
review aimed to critically evaluate the current status and future prospects of monoclonal antibody prophylaxis 
against P. falciparum infection in high-transmission settings, focusing on efficacy, safety, delivery platforms, and 
implementation challenges. A comprehensive literature search was conducted encompassing peer-reviewed clinical 
trials, systematic reviews, WHO reports, and preclinical studies published primarily within the last decade, 
addressing monoclonal antibodies targeting P. falciparum in endemic populations. Several long-acting mAbs 
targeting the circumsporozoite protein (CSP) of P. falciparum demonstrated high-level, durable protection 
exceeding 75% efficacy over transmission seasons following single-dose administration in adults and children. 
CIS43LS and related Fc-engineered antibodies show extended half-lives with successful intravenous and 
subcutaneous delivery, with manageable safety profiles including low incidence of infusion-related adverse events. 
Emerging candidates and newer antibodies targeting multiple epitopes hold promise for broader and longer-lasting 
efficacy. Challenges included optimizing dosing routes and schedules suitable for large-scale use, ensuring efficacy 
in vulnerable groups such as infants and pregnant women, cost considerations, and integration with existing malaria 
control interventions. Monoclonal antibodies represented a transformative prophylactic modality against P. 
falciparum in high-transmission settings, offering a potentially scalable complement to vaccines and 
chemoprevention. Continued clinical evaluation, refinement of delivery systems, and policy frameworks are essential 
to maximize the public health impact of this innovative approach.