The
malaria vaccine candidate
antigen, SE36, is based on the N-terminal 47 kDa domain of
Plasmodium falciparum serine repeat antigen 5 (SERA5). In epidemiological studies, we have previously shown the inhibitory effects of SE36 specific
antibodies on in vitro parasite growth and the negative correlation between antibody level and
malaria symptoms. A phase 1 b trial of the BK-SE36
vaccine in Uganda elicited 72% protective efficacy against symptomatic
malaria in children aged 6-20 years during the follow-up period 130-365 days post-second vaccination. Here, we performed
epitope mapping with synthetic
peptides covering the whole sequence of SE36 to identify and map dominant
epitopes in Ugandan adult serum presumed to have clinical immunity to P.
falciparum malaria. High titer sera from the Ugandan adults predominantly reacted with
peptides corresponding to two successive N-terminal regions of SERA5 containing octamer repeats and
serine rich sequences, regions of SERA5 that were previously reported to have limited polymorphism. Affinity purified
antibodies specifically recognizing the octamer repeats and
serine rich sequences exhibited a high antibody-dependent cellular inhibition (
ADCI) activity that inhibited parasite growth. Furthermore,
protein structure predictions and structural analysis of SE36 using spectroscopic methods indicated that N-terminal regions possessing inhibitory
epitopes are intrinsically unstructured. Collectively, these results suggest that strict tertiary structure of SE36
epitopes is not required to elicit protective
antibodies in naturally immune Ugandan adults.