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

Autor: Alan Aderem, Ulrike Wille-Reece, Ying Du, Christian F. Ockenhouse, Drew Dover, Ethan G. Thompson, Smitha Shankar, Joseph Valvo, Adrian V. S. Hill, Jenny Hendriks, W. Ripley Ballou, Erik Jongert, Jason A. Regules, Jackie Braun, Malcolm J. Gardner, Julius Muller, Robert A. van den Berg, Jerald C. Sadoff, Robbert van der Most, Daniel E. Zak
Rok vydání: 2020
Předmět:
lcsh:Immunologic diseases. Allergy
Myxovirus Resistance Proteins
0301 basic medicine
Plasmodium falciparum
Immunology
Protozoan Proteins
Antibodies
Protozoan

Biology
behavioral disciplines and activities
Receptors
G-Protein-Coupled

human challenge
Cohort Studies
03 medical and health sciences
Immunogenicity
Vaccine

0302 clinical medicine
Interferon
Malaria Vaccines
parasitic diseases
medicine
Humans
Immunology and Allergy
RNA-Seq
Malaria
Falciparum

Gene
systems vaccinology
Original Research
Infection Control
Vaccines
Synthetic

Vaccination
RTS
S

Antibody titer
vaccine correlates
medicine.disease
Virology
3. Good health
Titer
030104 developmental biology
Immunization
interferon response
Single-Cell Analysis
lcsh:RC581-607
Transcriptome
psychological phenomena and processes
Malaria
clinical immunology
030215 immunology
medicine.drug
Zdroj: Frontiers in Immunology
Frontiers in Immunology, Vol 11 (2020)
ISSN: 1664-3224
Popis: 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.
Databáze: OpenAIRE