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=8 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.