Apical Membrane Antigen 1 (AMA1) as a Vaccine Target Against Plasmodium knowlesi: Opportunities and Challenges

Abstract

Plasmodium knowlesi, the fifth human malaria parasite, has led to an emerging health crisis in Southeast Asia. P. knowlesi is an ideal vaccine target for its integral membrane protein, apical membrane antigen 1 (AMA1), which is critical for merozoite invasion of erythrocytes. Challenge studies in rhesus macaques show that recombinant PkAMA1 can elicit protective immunity and growth-inhibitory antibodies. The genetic diversity of PkAMA1 is lower than that of P. falciparum AMA1, which may facilitate the design of vaccines that are simpler and can induce cross-species protection. Some challenges include the need for high antibody levels, the possibility of strain-specific immune responses, and manufacturing complexity. This review covers the structural biology of PkAMA1, preclinical evidence supporting its potential as a vaccine target, and opportunities and strategies to make it a clinically viable intervention.