The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection.
Du Y., Thompson EG., Muller J., Valvo J., Braun J., Shankar S., van den Berg RA., Jongert E., Dover D., Sadoff J., Hendriks J., Gardner MJ., Ballou WR., Regules JA., van der Most R., Aderem A., Ockenhouse CF., Hill AV., Wille-Reece U., Zak DE.
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.