Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

Megan E Schmidt; David K Meyerholz; Steven M Varga

doi:10.1038/s41385-019-0243-4

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Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

Journal article

Open access

Peer reviewed

Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection

Megan E Schmidt, David K Meyerholz and Steven M Varga

Mucosal immunology, Vol.13(3), pp.507-517

05/2020

DOI: 10.1038/s41385-019-0243-4

PMCID: PMC7181396

PMID: 31844172

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Abstract

Despite being a leading cause of severe respiratory disease, there remains no licensed respiratory syncytial virus (RSV) vaccine. Neutralizing antibodies reduce the severity of RSV-associated disease, but are not sufficient for preventing reinfection. In contrast, the role of memory CD8 T cells in protecting against a secondary RSV infection is less established. We recently demonstrated that high-magnitude memory CD8 T cells efficiently reduced lung viral titers following RSV infection, but induced fatal immunopathology that was mediated by IFN-γ. To evaluate the ability of RSV-specific neutralizing antibodies to prevent memory CD8 T cell-mediated immunopathology, mice with high-magnitude memory CD8 T cell responses were treated with neutralizing antibodies prior to RSV challenge. Neutralizing antibody treatment significantly reduced morbidity and prevented mortality following RSV challenge compared with IgG-treated controls. Neutralizing antibody treatment restricted early virus replication, which caused a substantial reduction in memory CD8 T cell activation and IFN-γ production, directly resulting in survival. In contrast, therapeutic neutralizing antibody administration did not impact morbidity, mortality, or IFN-γ levels, despite significantly reducing lung viral titers. Therefore, only pre-existing neutralizing antibodies prevent memory CD8 T cell-mediated immunopathology following RSV infection. Overall, our results have important implications for the development of future RSV vaccines.

Animals

Antibodies, Neutralizing - immunology

Antibodies, Neutralizing - pharmacology

Antibodies, Viral - immunology

Antibodies, Viral - pharmacology

Biopsy

CD8-Positive T-Lymphocytes - drug effects

CD8-Positive T-Lymphocytes - immunology

CD8-Positive T-Lymphocytes - metabolism

Disease Models, Animal

Disease Susceptibility - immunology

Female

Host-Pathogen Interactions - immunology

Immunization

Immunologic Memory

Interferon-gamma - metabolism

Mice

Prognosis

Respiratory Syncytial Virus Infections - immunology

Respiratory Syncytial Virus Infections - metabolism

Respiratory Syncytial Virus Infections - pathology

Respiratory Syncytial Virus Infections - virology

Respiratory Syncytial Viruses - immunology

Details

Title: Subtitle: Pre-existing neutralizing antibodies prevent CD8 T cell-mediated immunopathology following respiratory syncytial virus infection
Creators: Megan E Schmidt - University of Iowa
David K Meyerholz - University of Iowa
Steven M Varga - University of Iowa
Resource Type: Journal article
Publication Details: Mucosal immunology, Vol.13(3), pp.507-517
DOI: 10.1038/s41385-019-0243-4
PMID: 31844172
PMCID: PMC7181396
NLM abbreviation: Mucosal Immunol
ISSN: 1933-0219
eISSN: 1935-3456
Grant note: T32 AI007485 / NIAID NIH HHS R01 AI124093 / NIAID NIH HHS
Language: English
Date published: 05/2020
Academic Unit: Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Community and Behavioral Health
Record Identifier: 9984186681702771

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14 Times Cited - Web of Science