AUTHOR=van den Berg Robert A. , Coccia Margherita , Ballou W. Ripley , Kester Kent E. , Ockenhouse Christian F. , Vekemans Johan , Jongert Erik , Didierlaurent Arnaud M. , van der Most Robbert G. 

TITLE=Predicting RTS,S Vaccine-Mediated Protection from Transcriptomes in a Malaria-Challenge Clinical Trial

JOURNAL=Frontiers in Immunology

VOLUME=Volume 8 - 2017

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00557

DOI=10.3389/fimmu.2017.00557

ISSN=1664-3224

ABSTRACT=The RTS,S candidate malaria vaccine can protect against controlled human malaria infection (CHMI), but how protection is achieved remains unclear. Here we have analyzed longitudinal peripheral-blood transcriptome and immunogenicity data from a clinical efficacy trial in which healthy adults received three RTS,S doses 4-weeks apart followed by CHMI 2-weeks later. Multiway partial-least-squares discriminant analysis (N-PLS-DA) of transcriptome data identified 110 genes that could be used in predictive models of protection. Among the 110 genes, 42 had known immune-related functions; including 29 that were related to the NF-κB-signaling pathway and 14 to the IFN-γ-signaling pathway. Post-dose 3 serum-IFN-γ concentrations were also correlated with protection; and N-PLS-DA of IFN-γ-signaling pathway transcriptome data selected almost all (44/45) of the representative genes for predictive models of protection. Hence the identification of the NF-κB and IFN-γ pathways provides further insight into how vaccine-mediated protection may be achieved.