Frontiers in Immunology (Apr 2020)

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

  • 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

DOI
https://doi.org/10.3389/fimmu.2020.00669
Journal volume & issue
Vol. 11

Abstract

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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.

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