Plasmodium vivax serological exposure markers: PvMSP1-42-induced humoral and memory B-cell response generates long-lived antibodies

by Feng Lu, Jiahui Xu, Yaobao Liu, Zhenyu Ren, Junhu Chen, Weijuan Gong, Yi Yin, Yinyue Li, Li Qian, Xinlong He, Xiu Han, Zhijie Lin, Jingyuan Lu, Wenwen Zhang, Jiali Liu, Didier Menard, Eun-Taek Han, Jun Cao

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73⁺CD80⁺ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.