In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2022-11-15), p. e1010968-
Abstract:
Successive episodes of hepatitis C virus (HCV) infection represent a unique natural rechallenge experiment to define correlates of long-term protective immunity and inform vaccine development. We applied a systems immunology approach to characterize longitudinal changes in the peripheral blood transcriptomic signatures in eight subjects who spontaneously resolved two successive HCV infections. Furthermore, we compared these signatures with those induced by an HCV T cell-based vaccine regimen. We identified a plasma cell transcriptomic signature during early acute HCV reinfection. This signature was absent in primary infection and following HCV vaccine boost. Spontaneous resolution of HCV reinfection was associated with rapid expansion of glycoprotein E2-specifc memory B cells in three subjects and transient increase in E2-specific neutralizing antibodies in six subjects. Concurrently, there was an increase in the breadth and magnitude of HCV-specific T cells in 7 out of 8 subjects. These results suggest a cooperative role for both antibodies and T cells in clearance of HCV reinfection and support the development of next generation HCV vaccines targeting these two arms of the immune system.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010968
DOI:
10.1371/journal.ppat.1010968.g001
DOI:
10.1371/journal.ppat.1010968.g002
DOI:
10.1371/journal.ppat.1010968.g003
DOI:
10.1371/journal.ppat.1010968.g004
DOI:
10.1371/journal.ppat.1010968.t001
DOI:
10.1371/journal.ppat.1010968.s001
DOI:
10.1371/journal.ppat.1010968.s002
DOI:
10.1371/journal.ppat.1010968.s003
DOI:
10.1371/journal.ppat.1010968.s004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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