Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis

MSphere
Joshua M ObieroPhilip L Felgner

Abstract

Immunization with sporozoites under chloroquine chemoprophylaxis (CPS) induces distinctly preerythrocytic and long-lasting sterile protection against homologous controlled human malaria infection (CHMI). To identify possible humoral immune correlates of protection, plasma samples were collected from 38 CPS-immunized Dutch volunteers for analysis using a whole Plasmodium falciparum proteome microarray with 7,455 full-length or segmented protein features displaying about 91% of the total P. falciparum proteome. We identified 548 reactive antigens representing 483 unique proteins. Using the breadth of antibody responses for each subject in a mixture-model algorithm, we observed a trimodal pattern, with distinct groups of 16 low responders, 19 medium responders, and 3 high responders. Fifteen out of 16 low responders, 12 of the 19 medium responders, and 3 out of 3 high responders were fully protected from a challenge infection. In the medium-responder group, we identified six novel antigens associated with protection (area under the curve [AUC] value of ≥0.75; P < 0.05) and six other antigens that were specifically increased in nonprotected volunteers (AUC value of ≤0.25; P < 0.05). When used in combination, the multiantigen classi...Continue Reading

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Citations

Mar 29, 2019·MSphere·Lars Hviid
Jan 12, 2021·Expert Review of Vaccines·Reshma J NevagiDanielle I Stanisic
Aug 22, 2020·Current Opinion in Immunology·Cevayir Coban
Aug 3, 2021·Frontiers in Immunology·Alejandro D RicciFernán Agüero

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Methods Mentioned

BETA
in vitro transcription
RNA-Seq
PCR
protein array

Clinical Trials Mentioned

NCT00442377
NCT01236612
NCT01218893

Software Mentioned

PlasmoDB
ggplot2
R
R package “ scales
R package “ mixtools ”

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