DOI: 10.5061/dryad.n1m33qq
title: Data from: Functional antibodies against Plasmodium falciparum sporozoites are associated with a longer time to qPCR-detected infection among schoolchildren in Burkina Faso

description: Background: Individuals living in malaria-endemic regions develop
 naturally acquired immunity against severe malarial disease, but it is
 unclear whether immunity that affects the establishment of infections
 develops following continuous natural exposure. Methods: We cleared
 schoolchildren in Burkina Faso of possible sub-patent infections and
 examined them weekly for incident infections by PCR. Plasma samples
 collected at enrolment were used to quantify antibodies to the
 pre-eryhrocytic-stage antigens circumsporozoite protein (CSP) and liver
 stage antigen. Sporozoite gliding inhibition by naturally acquired
 antibodies was assessed using Plasmodium falciparum NF54 sporozoites;
 hepatocyte invasion was assessed using the human HC-04 hepatoma cell line
 and NF54 sporozoites. The associations between these functional
 pre-erythrocytic immunity phenotypes and time to PCR-detected infection
 were studied. Results: A total of 51 children were monitored; the median
 time to first detection of infection by PCR or development of clinical
 symptoms was 28 days. Anti-CSP antibody titres showed a strong positive
 association with sporozoite gliding motility inhibition (P&lt;0.0001,
 Spearman’s ρ=0.76). In vitro hepatocyte invasion was inhibited by
 naturally acquired antibodies (median invasion inhibition, 19.4% [IQR
 15.2-40.9%]), and there was a positive correlation between gliding and
 invasion inhibition (P=0.02, Spearman’s ρ=0.60). Survival analysis
 indicated longer time to infection in individuals displaying
 higher-than-median sporozoite gliding inhibition activity (P=0.01).
 Conclusions: In summary, functional antibodies against the
 pre-erythrocytic stages of malaria infection are acquired in children who
 are repeatedly exposed to Plasmodium parasites. This immune response does
 not prevent them from becoming infected during a malaria transmission
 season, but might delay the appearance of blood stage parasitaemia and
 consequently needs to be considered in the evaluation of malaria vaccines.
description: Sensitivity
 AnalysisThis file describes
 additional survival analyses that show that functional responses against
 pre-erythrocytic stages are also associated with infection risk when
 different parasite density thresholds are used to define
 infection.Sensitivity_Analysis.docxLegends of supplementary figuresThe file contains the legends of supplementary figures S1 to S5.Legends_v2.docxFigure S1Correlation analyses of naturally acquired sporozoite-specific IgG and IgM antibodiesFigure_S1.docxFigure S2Antibody specificity and in vitro gliding inhibition by naturally acquired antibodies.Revised_Figure_S2.docxFigure S3Inhibition of in vitro sporozoite invasion of hepatocytes by antibodies from children in Burkina Faso.Revised_Figure_S3.docxFigure S4CSP antibody levels versus immune responses against asexual stage antigens.New_Figure_S4.docxFigure S5Distribution of immune phenotypes.Figure_S5.docxData used in survival analysisThis file contains the data used in the survival analysis. There are 6 variables and 51 observations, corresponding to the 51 study participants included in this analysis. The variable 'Delay' represents the time to infection detection. The variable 'Infection' has value 1 if the study participant had infection detected during follow-up. The other variables represent results of immunological assays.Data.xlsxELISA and sporozoite gliding inhibition dataThis file contains individual-level data on antibody titers against circumsporozoite protein (CSP), Liver stage antigen-1 (LSA-1) and asexual parasite lysate as well as functional data on sporozoite gliding inhibition