Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Human infection challenge permits in-depth, early, and pre-symptomatic characterization of the immune response, enabling the identification of factors that are important for viral clearance. Here, we performed intranasal inoculation of 34 young adult, seronegative volunteers with a pre-Alpha severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain. Of these participants, 18 (53%) became infected and showed an interferon-dominated mediator response with divergent kinetics between nasal and systemic sites. Peripheral CD4+ and CD8+ T cell activation and proliferation were early and robust but showed distinct kinetic and phenotypic profiles; antigen-specific T cells were largely CD38+Ki67+ and displayed central and effector memory phenotypes. Both mucosal and systemic antibodies became detectable around day 10, but nasal antibodies plateaued after day 14 while circulating antibodies continued to rise. Intensively granular measurements in nasal mucosa and blood allowed modeling of immune responses to primary SARS-CoV-2 infection that revealed CD8+ T cell responses and early mucosal IgA responses strongly associated with viral control, indicating that these mechanisms should be targeted for transmission-reducing intervention.
Date Issued
2024-02
Date Acceptance
2024-01-12
Citation
Science Immunology, 2024, 9 (92)
ISSN
2470-9468
Publisher
American Association for the Advancement of Science
Journal / Book Title
Science Immunology
Volume
9
Issue
92
Copyright Statement
Copyright © 2024 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. This is the author’s accepted manuscript made available under a CC-BY licence in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy)
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/38335268
Subjects
CD8-Positive T-Lymphocytes
COVID-19
Humans
Nasal Mucosa
SARS-CoV-2
Vaccination
Publication Status
Published
Coverage Spatial
United States
Article Number
eadj9285
Date Publish Online
2024-02-09