Controlled human malaria infection in adults identify combinations of merozoite antigens associated with clinical immunity
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Two vaccines are currently licensed against Plasmodium falciparum malaria but offer only partial protection that wanes, necessitating repeated dosing that is challenging to implement where it is needed most. We previously identified a subset of Kenyan adults with naturally acquired clinical immunity using controlled human malaria infection studies (CHMI, n = 86/142; ClinicalTrials.gov - NCT02739763). Subsequent studies showed that clinical immunity was strongly correlated with IgG Fc-mediated functional activity against whole merozoites. Here, to zoom in on specific targets associated with clinical immunity, we use samples from the CHMI study and a custom protein microarray (KILchip) to measure IgG antibody reactivity against seventy recombinant merozoite antigens. We identify the top-ranking antigens by analyzing the data using five distinct statistical methodologies: the nonparametric Wilcoxon rank sum test, a Cox proportional hazards model, a modified Poisson regression model, and the machine learning Least Absolute Shrinkage and Selection Operator (LASSO) and random forest models. Antibodies against MSP1, MSP11, RAMA, MSP7, PF3D7_1401600 (PHISTB) and PTEX150 were consistently associated with clinical immunity and in combination predicted complete protection. These findings may be useful to prioritize the next generation of malaria blood stage vaccine candidates.
Date Issued
2026-07-17
Date Acceptance
2026-04-22
Citation
Nature Communications, 2026, 17
ISSN
2041-1723
Publisher
Nature Portfolio
Journal / Book Title
Nature Communications
Volume
17
Copyright Statement
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
10.1038/s41467-026-72716-x
Publication Status
Published
Article Number
ARTN 6472
Date Publish Online
2026-05-05