LARC-GAPs: emerging whole-sporozoite vaccines for high-level sterile protection against malaria

Malaria remains a major global health challenge. Despite the recent deployment of the RTS,S/AS01 and R21/Matrix-M vaccines, malaria cases and deaths continue to increase. Although these vaccines are a major achievement, their protection is incomplete and wanes over time. Whole-sporozoite vaccines are the most effective malaria vaccines targeting the pre-erythrocytic stage. Among them, genetically attenuated parasites (GAPs) have shown advantages over other vaccine approaches. Recent studies have shown that late liver-stage-arresting, replication-competent (LARC)-GAPs elicit broader immune responses and provide better protection than other malaria vaccines. Here, we highlight the development of GAP vaccines, compare early-arresting GAPs and LARC-GAPs, discuss recent clinical data, and assess their translational potential as next-generation malaria vaccines.