Controlled human malaria infection in adults identify combinations of merozoite antigens associated with clinical immunity
Abstract
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.
Article Details
Authors (48)
Irene N. Nkumama
Kennedy Mwai
Dennis Odera
Lydia Nyamako
Kristin Fürle
Micha Rosenkranz
Rinter Kimathi
Patricia Njuguna
B. Kim Lee Sim
Mainga Hamaluba
Kenya Medical Research Institute–Wellcome Trust Research Program, Kilifi
Roland Frank
Zaydah de Laurent
Silvia Kariuki
Domitila Kimani
Khadija Said Mohammed
Moses Mosobo
Abdirahman I. Abdi
Donwilliams Omuoyo
Edward Otieno
Jimmy Shangala
Kenya Medical Research Institute–Wellcome Trust Research Program, Kilifi
Juliana Wambua
Janet Musembi
Jennifer Musyoki
Michelle Muthui
Jedidah Mwacharo
Francis Ndungu
Joyce M. Ngoi
Johnstone Makale
Rodney Ogwang
Omar Ngoto
Dennis O. Odera
Yonas Abebe
Thomas L. Richie
Peter F. Billingsley
Stephen L. Hoffman
Eric R. James
Kevin Marsh
John Ong’echa
Peter C. Bull
Sam Kinyanjui
Cheryl Kivisi
Bernhards Ogutu
Fredrick Olewe
Thomas N. Williams
Imperial College, London
Melissa C. Kapulu
Philip Bejon
James Tuju
Faith H. A. Osier