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.
Keywords: clinical immunology; human challenge; interferon response; malaria vaccines; systems vaccinology; vaccine correlates.
Copyright © 2020 Du, Thompson, Muller, Valvo, Braun, Shankar, van den Berg, Jongert, Dover, Sadoff, Hendriks, Gardner, Ballou, Regules, van der Most, Aderem, Ockenhouse, Hill, Wille-Reece and Zak.