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Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects

Mazouz, S; Salinas, E; Bédard, N; Filali, A; Khedr, O; Swadling, L; Abdel-Hakeem, MS; ... Shoukry, NH; + view all (2022) Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects. PLoS Pathogens , 18 (11) , Article e1010968. 10.1371/journal.ppat.1010968. Green open access

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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. (175 words).

Type: Article
Title: Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.ppat.1010968
Publisher version: https://doi.org/10.1371/journal.ppat.1010968
Language: English
Additional information: © 2022 Mazouz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Humans, Antibodies, Neutralizing, Hepacivirus, Hepatitis C, Hepatitis C Antibodies, Reinfection, Transcriptome, Viral Envelope Proteins, Viral Hepatitis Vaccines
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10161744
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