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:10.3389/fimmu.2020.00669

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

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.

Original language	English
Article number	669
Journal	Frontiers in Immunology
Volume	11
DOIs	https://doi.org/10.3389/fimmu.2020.00669
State	Published - 28 Apr 2020
Externally published	Yes

Keywords

clinical immunology
human challenge
interferon response
malaria vaccines
systems vaccinology
vaccine correlates

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10.3389/fimmu.2020.00669

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Du, Y., Thompson, E. G., Muller, J., Valvo, J., Braun, J., Shankar, S., van den Berg, R. A., Jongert, E., Dover, D., Sadoff, J., Hendriks, J., Gardner, M. J., Ballou, W. R., Regules, J. A., van der Most, R., Aderem, A., Ockenhouse, C. F., Hill, A. V., Wille-Reece, U., & Zak, D. E. (2020). The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection. Frontiers in Immunology, 11, Article 669. https://doi.org/10.3389/fimmu.2020.00669

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

abstract = "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",

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

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 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.",

year = "2020",

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doi = "10.3389/fimmu.2020.00669",

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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 2020, 'The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection', Frontiers in Immunology, vol. 11, 669. https://doi.org/10.3389/fimmu.2020.00669

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T1 - The Ratiometric Transcript Signature MX2/GPR183 Is Consistently Associated With RTS,S-Mediated Protection Against Controlled Human Malaria Infection

AU - Du, Ying

AU - Thompson, Ethan G.

AU - Muller, Julius

AU - Valvo, Joseph

AU - Braun, Jackie

AU - Shankar, Smitha

AU - van den Berg, Robert A.

AU - Jongert, Erik

AU - Dover, Drew

AU - Sadoff, Jerald

AU - Hendriks, Jenny

AU - Gardner, Malcolm J.

AU - Ballou, W. Ripley

AU - Regules, Jason A.

AU - van der Most, Robbert

AU - Aderem, Alan

AU - Ockenhouse, Christian F.

AU - Hill, Adrian V.

AU - Wille-Reece, Ulrike

AU - Zak, Daniel E.

N1 - Publisher Copyright: © 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.

PY - 2020/4/28

Y1 - 2020/4/28

N2 - 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.

AB - 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.

KW - clinical immunology

KW - human challenge

KW - interferon response

KW - malaria vaccines

KW - systems vaccinology

KW - vaccine correlates

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U2 - 10.3389/fimmu.2020.00669

DO - 10.3389/fimmu.2020.00669

M3 - Article

C2 - 32411130

AN - SCOPUS:85084523495

SN - 1664-3224

VL - 11

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 669

ER -

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

Abstract

Keywords

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