| dc.description.abstract |
A signature remains elusive of naturally-acquired immunity against Plasmodium falciparum.
We identified P. falciparum in a 14-month cohort of 239 people in Kenya, genotyped at
immunogenic parasite targets expressed in the pre-erythrocytic (circumsporozoite protein,
CSP) and blood (apical membrane antigen 1, AMA-1) stages, and classified into epitope
type based on variants in the DV10, Th2R, and Th3R epitopes in CSP and the c1L region of
AMA-1. Compared to asymptomatic index infections, symptomatic malaria was associated
with reduced reinfection by parasites bearing homologous CSP-Th2R (adjusted hazard
ratio [aHR]:0.63; 95% CI:0.45–0.89; p = 0.008) CSP-Th3R (aHR:0.71; 95% CI:0.52–0.97; p
= 0.033), and AMA-1 c1L (aHR:0.63; 95% CI:0.43–0.94; p = 0.022) epitope types. The asso-
ciation of symptomatic malaria with reduced hazard of homologous reinfection was stron-
gest for rare epitope types. Symptomatic malaria provides more durable protection against
reinfection with parasites bearing homologous epitope types. The phenotype represents a
legible molecular epidemiologic signature of naturally-acquired immunity by which to identify
new antigen targets. |
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