AUTHOR=Du Ying , Thompson Ethan G. , Muller Julius , Valvo Joseph , Braun Jackie , Shankar Smitha , van den Berg Robert A. , Jongert Erik , Dover Drew , Sadoff Jerald , Hendriks Jenny , Gardner Malcolm J. , Ballou W. Ripley , Regules Jason A. , van der Most Robbert , Aderem Alan , Ockenhouse Christian F. , Hill Adrian V. , Wille-Reece Ulrike , Zak Daniel E. 

TITLE=The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.00669

DOI=10.3389/fimmu.2020.00669

ISSN=1664-3224

ABSTRACT=<p>The RTS,S/AS01 vaccine provides partial protection against <italic>Plasmodium falciparum</italic> infection but determinants of protection and/or disease are unclear. Previously, anti-circumsporozoite protein (CSP) antibody titers and blood RNA signatures were associated with RTS,S/AS01 efficacy against controlled human malaria infection (CHMI). By analyzing host blood transcriptomes from five RTS,S vaccination CHMI studies, we demonstrate that the transcript ratio MX2/GPR183, measured 1 day after third immunization, discriminates protected from non-protected individuals. This ratiometric signature provides information that is complementary to anti-CSP titer levels for identifying RTS,S/AS01 immunized people who developed protective immunity and suggests a role for interferon and oxysterol signaling in the RTS,S mode of action.</p>