Differential immune transcriptomic profiles between vaccinated and resolved HCV reinfected subjects

• Type of Material: Article
• Authors: Sabrina Mazouz, entre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Eduardo Salinas, Emory University; Nathalie Bedard, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Ali Filali, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Omar Khedr, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Leo Swadling, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Mohamed S Abdel-Hakeem, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Asiyah Siddique, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Eleanor Barnes, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Julie Bruneau, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Arash Grakoui, Emory University; Naglaa H Shoukry, Centre de Recherche du Centre hospitalier de l’Université de Montréal (CRCHUM); Mohamed Abdel Hakeem, Emory University
• Language: English
• Date: 2022-11-01
• Publisher: PUBLIC LIBRARY SCIENCE
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Mazouz et al
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1371/journal.ppat.1010968
• Title of Journal or Parent Work: PLOS PATHOGENS
• Volume: 18
• Issue: 11
• Start Page: e1010968
• End Page: e1010968
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health (NIH) U01AI131313 to NHS, R01AI136533 and U19AI159819 to NHS and AG, ORIP/OD P51OD011132 (formerly NCRR P51RR000165) to the Emory National Primate Research Center (AG), the Canadian Institutes of Health Research (CIHR) (PJT-173467) to NHS and JB, and Fonds de recherche du Québec–Santé (FRQS) AIDS and Infectious Disease Network (Réseau SIDA-MI). SM is supported by a doctoral fellowship from the Canadian Network on Hepatitis C (CanHepC). CanHepC is funded by a joint initiative of CIHR (HPC-178912) and the Public Health Agency of Canada. MSA received doctoral fellowships from CIHR and CanHepC. EB was funded by the Medical Research Council UK, the Oxford NIHR Biomedical Research Centre and is an NIHR Senior Investigator.JB is the Canada Research Chair in Addiction Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
• Keywords: RESPONSES; Virology; SYSTEMS BIOLOGY; CLEARANCE; INNATE; Microbiology; IMMUNOGENICITY; VIRUS-INFECTION; HEPATITIS-C INFECTION; YELLOW-FEVER VACCINE; Parasitology; Life Sciences & Biomedicine; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery

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).