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

• Main Authors: Ying Du, Ethan G. Thompson, Julius Muller, Joseph Valvo, Jackie Braun, Smitha Shankar, Robert A. van den Berg, Erik Jongert, Drew Dover, Jerald Sadoff, Jenny Hendriks, Malcolm J. Gardner, W. Ripley Ballou, Jason A. Regules, Robbert van der Most, Alan Aderem, Christian F. Ockenhouse, Adrian V. Hill, Ulrike Wille-Reece, Daniel E. Zak
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-04-01
• Series: Frontiers in Immunology
• Subjects: malaria vaccines; clinical immunology; vaccine correlates; human challenge; systems vaccinology; interferon response
• Online Access: https://www.frontiersin.org/article/10.3389/fimmu.2020.00669/full
• ISSN: 1664-3224

The RTS,S/AS01 vaccine provides partial protection against Plasmodium falciparum 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.