Joyner CJ, Brito CFA, Saney CL, et al. - Using the P. cynomolgi–rhesus macaque model of relapsing malaria, researchers sought to ascertain whether a single sporozoite-initiated blood-stage infection can lead to clinical immunity which could prevent illness during relapses and homologous reinfections. Data integration was done from whole blood RNA-sequencing, flow cytometry, P. cynomolgi-specific ELISAs, and opsonic phagocytosis assays. The analysis revealed an association of this immunity with a rapid recall response by memory B cells that expand and produce anti-parasite IgG1 that can mediate parasite clearance of relapsing parasites. During relapses, parasitemia reduction was reflected by a reduction in the total number of circulating gametocytes, but there was an increase in the cumulative proportion of gametocytes during relapses. Overall, macaques may display clinically silent P. cynomolgi relapse infections due to rapid memory B cell responses that support to clear asexual-stage parasites but yet carry gametocytes. Findings thereby present mechanistic insights into the host-parasite interface during Plasmodium relapse infections and exhibit that gametocytes could be present in clinically silent relapses that may be infectious to mosquitoes.