The malaria vaccine BK-SE36 is a recombinant protein (SE36) based on the Honduras 1 serine repeat antigen-5 of Plasmodium falciparum, adsorbed to aluminium hydroxide gel. The phase Ib trial in Uganda demonstrated the safety and immunogenicity of BK-SE36. Ancillary analysis in the follow-up study of 6-20 year-old volunteers suggest significant differences in time to first episodes of clinical malaria in vaccinees compared to placebo/control group. Here, we aimed to get further insights into the association of anti-SE36 antibody titres and natural P. falciparum infection. Children who received BK-SE36 and whose antibody titres against SE36 increased by ≥1.92-fold after vaccination were categorised as responders. Most responders did not have or only had a single episode of natural P. falciparum infection. Notably, responders who did not experience infection had relatively high anti-SE36 antibody titres post-second vaccination compared to those who were infected. The anti-SE36 antibody titres of the responders who experienced malaria were boosted after infection and they had lower risk of reinfection. These findings show that anti-SE36 antibody titres induced by BK-SE36 vaccination offered protection against malaria. The vaccine is now being evaluated in a phase Ib trial in children less than 5 years old.