In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 19, No. 5 ( 2023-5-17), p. e1011051-
Abstract:
Understanding immune mechanisms that mediate malaria protection is critical for improving vaccine development. Vaccination with radiation-attenuated Plasmodium falciparum sporozoites (PfRAS) induces high level of sterilizing immunity against malaria and serves as a valuable tool for the study of protective mechanisms. To identify vaccine-induced and protection-associated responses during malarial infection, we performed transcriptome profiling of whole blood and in-depth cellular profiling of PBMCs from volunteers who received either PfRAS or noninfectious mosquito bites, followed by controlled human malaria infection (CHMI) challenge. In-depth single-cell profiling of cell subsets that respond to CHMI in mock-vaccinated individuals showed a predominantly inflammatory transcriptome response. Whole blood transcriptome analysis revealed that gene sets associated with type I and II interferon and NK cell responses were increased in prior to CHMI while T and B cell signatures were decreased as early as one day following CHMI in protected vaccinees. In contrast, non-protected vaccinees and mock-vaccinated individuals exhibited shared transcriptome changes after CHMI characterized by decreased innate cell signatures and inflammatory responses. Additionally, immunophenotyping data showed different induction profiles of vδ2+ γδ T cells, CD56+ CD8+ T effector memory (Tem) cells, and non-classical monocytes between protected vaccinees and individuals developing blood-stage parasitemia, following treatment and resolution of infection. Our data provide key insights in understanding immune mechanistic pathways of PfRAS-induced protection and infective CHMI. We demonstrate that vaccine-induced immune response is heterogenous between protected and non-protected vaccinees and that inducted-malaria protection by PfRAS is associated with early and rapid changes in interferon, NK cell and adaptive immune responses. Trial Registration : ClinicalTrials.gov NCT01994525 .
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1011051
DOI:
10.1371/journal.ppat.1011051.g001
DOI:
10.1371/journal.ppat.1011051.g002
DOI:
10.1371/journal.ppat.1011051.g003
DOI:
10.1371/journal.ppat.1011051.g004
DOI:
10.1371/journal.ppat.1011051.g005
DOI:
10.1371/journal.ppat.1011051.g006
DOI:
10.1371/journal.ppat.1011051.s001
DOI:
10.1371/journal.ppat.1011051.s002
DOI:
10.1371/journal.ppat.1011051.s003
DOI:
10.1371/journal.ppat.1011051.s004
DOI:
10.1371/journal.ppat.1011051.s005
DOI:
10.1371/journal.ppat.1011051.s006
DOI:
10.1371/journal.ppat.1011051.s007
DOI:
10.1371/journal.ppat.1011051.s008
DOI:
10.1371/journal.ppat.1011051.s009
DOI:
10.1371/journal.ppat.1011051.s010
DOI:
10.1371/journal.ppat.1011051.s011
DOI:
10.1371/journal.ppat.1011051.s012
DOI:
10.1371/journal.ppat.1011051.s013
DOI:
10.1371/journal.ppat.1011051.s014
DOI:
10.1371/journal.ppat.1011051.s015
DOI:
10.1371/journal.ppat.1011051.r001
DOI:
10.1371/journal.ppat.1011051.r002
DOI:
10.1371/journal.ppat.1011051.r003
DOI:
10.1371/journal.ppat.1011051.r004
DOI:
10.1371/journal.ppat.1011051.r005
DOI:
10.1371/journal.ppat.1011051.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2023
detail.hit.zdb_id:
2205412-1
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