Tissue-dependent protection mechanisms of antibodies targeting Plasmodium sporozoites

Malaria remains a major global health burden. Antibodies targeting the circumsporozoite protein (CSP), the main surface protein of Plasmodium sporozoites, have emerged as a promising prophylactic tool. Antibodies that bind to the CSP central repetitive region are the foundation of protection against sporozoite infection elicited by CSP-based vaccines. These antibodies have been shown to provide protection in both animal models and humans, although how they confer protection is not fully understood. This review explores how anti-CSP antibodies can neutralize sporozoites and how they mediate protection through tissue-specific mechanisms. Understanding these multilayered mechanisms is critical for improving vaccines and antibody-based prophylaxis.