T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

Bruno Salaun; Jonathan De Smedt; Charlotte Vernhes; Annick Moureau; Deniz Öner; Arangassery Rosemary Bastian; Michel Janssens; Sunita Balla-Jhagjhoorsingh; Jeroen Aerssens; Christophe Lambert; Samuel Coenen; Christopher C Butler; Simon B Drysdale; Joanne G Wildenbeest; Andrew J Pollard; Peter J M Openshaw; Louis Bont

doi:10.3389/fimmu.2023.1260146

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

Bruno Salaun^*, Jonathan De Smedt, Charlotte Vernhes, Annick Moureau, Deniz Öner, Arangassery Rosemary Bastian, Michel Janssens, Sunita Balla-Jhagjhoorsingh, Jeroen Aerssens, Christophe Lambert, Samuel Coenen, Christopher C Butler, Simon B Drysdale, Joanne G Wildenbeest, Andrew J Pollard, Peter J M Openshaw, Louis Bont

^*Corresponding author for this work

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Abstract

INTRODUCTION: The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.

METHODS: This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.

RESULTS: Pre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).

CONCLUSION: The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.

Original language	English
Article number	1260146
Number of pages	11
Journal	Frontiers in Immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1260146
Publication status	Published - 13 Oct 2023

Keywords

CD4+ T cell
T-cell memory
antibody function
cell-mediated immunity
correlate of protection
interferon-gamma
machine learning
respiratory syncytial virus

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Salaun, B., De Smedt, J., Vernhes, C., Moureau, A., Öner, D., Bastian, A. R., Janssens, M., Balla-Jhagjhoorsingh, S., Aerssens, J., Lambert, C., Coenen, S., Butler, C. C., Drysdale, S. B., Wildenbeest, J. G., Pollard, A. J., Openshaw, P. J. M., & Bont, L. (2023). T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults. Frontiers in Immunology, 14, Article 1260146. https://doi.org/10.3389/fimmu.2023.1260146

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title = "T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults",

abstract = "INTRODUCTION: The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.METHODS: This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.RESULTS: Pre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).CONCLUSION: The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.",

keywords = "CD4+ T cell, T-cell memory, antibody function, cell-mediated immunity, correlate of protection, interferon-gamma, machine learning, respiratory syncytial virus",

author = "Bruno Salaun and {De Smedt}, Jonathan and Charlotte Vernhes and Annick Moureau and Deniz {\"O}ner and Bastian, {Arangassery Rosemary} and Michel Janssens and Sunita Balla-Jhagjhoorsingh and Jeroen Aerssens and Christophe Lambert and Samuel Coenen and Butler, {Christopher C} and Drysdale, {Simon B} and Wildenbeest, {Joanne G} and Pollard, {Andrew J} and Openshaw, {Peter J M} and Louis Bont",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 Salaun, De Smedt, Vernhes, Moureau, {\"O}ner, Bastian, Janssens, Balla-Jhagjhoorsingh, Aerssens, Lambert, Coenen, Butler, Drysdale, Wildenbeest, Pollard, Openshaw and Bont.",

year = "2023",

month = oct,

day = "13",

doi = "10.3389/fimmu.2023.1260146",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S. A.",

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Salaun, B, De Smedt, J, Vernhes, C, Moureau, A, Öner, D, Bastian, AR, Janssens, M, Balla-Jhagjhoorsingh, S, Aerssens, J, Lambert, C, Coenen, S, Butler, CC, Drysdale, SB, Wildenbeest, JG, Pollard, AJ, Openshaw, PJM & Bont, L 2023, 'T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults', Frontiers in Immunology, vol. 14, 1260146. https://doi.org/10.3389/fimmu.2023.1260146

TY - JOUR

T1 - T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

AU - Salaun, Bruno

AU - De Smedt, Jonathan

AU - Vernhes, Charlotte

AU - Moureau, Annick

AU - Öner, Deniz

AU - Bastian, Arangassery Rosemary

AU - Janssens, Michel

AU - Balla-Jhagjhoorsingh, Sunita

AU - Aerssens, Jeroen

AU - Lambert, Christophe

AU - Coenen, Samuel

AU - Butler, Christopher C

AU - Drysdale, Simon B

AU - Wildenbeest, Joanne G

AU - Pollard, Andrew J

AU - Openshaw, Peter J M

AU - Bont, Louis

N1 - Publisher Copyright: Copyright © 2023 Salaun, De Smedt, Vernhes, Moureau, Öner, Bastian, Janssens, Balla-Jhagjhoorsingh, Aerssens, Lambert, Coenen, Butler, Drysdale, Wildenbeest, Pollard, Openshaw and Bont.

PY - 2023/10/13

Y1 - 2023/10/13

N2 - INTRODUCTION: The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.METHODS: This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.RESULTS: Pre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).CONCLUSION: The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.

AB - INTRODUCTION: The immune mechanisms supporting partial protection from reinfection and disease by the respiratory syncytial virus (RSV) have not been fully characterized. In older adults, symptoms are typically mild but can be serious in patients with comorbidities when the infection extends to the lower respiratory tract.METHODS: This study formed part of the RESCEU older-adults prospective-cohort study in Northern Europe (2017-2019; NCT03621930) in which a thousand participants were followed over an RSV season. Peripheral-blood samples (taken pre-season, post-season, during illness and convalescence) were analyzed from participants who (i) had a symptomatic acute respiratory tract infection by RSV (RSV-ARTI; N=35) or (ii) asymptomatic RSV infection (RSV-Asymptomatic; N=16). These analyses included evaluations of antibody (Fc-mediated-) functional features and cell-mediated immunity, in which univariate and machine-learning (ML) models were used to explore differences between groups.RESULTS: Pre-RSV-season peripheral-blood biomarkers were predictive of symptomatic RSV infection. T-cell data were more predictive than functional antibody data (area under receiver operating characteristic curve [AUROC] for the models were 99% and 76%, respectively). The pre-RSV season T-cell phenotypes which were selected by the ML modelling and which were more frequent in RSV-Asymptomatic group than in the RSV-ARTI group, coincided with prominent phenotypes identified during convalescence from RSV-ARTI (e.g., IFN-γ+, TNF-α+ and CD40L+ for CD4+, and IFN-γ+ and 4-1BB+ for CD8+).CONCLUSION: The evaluation and statistical modelling of numerous immunological parameters over the RSV season suggests a primary role of cellular immunity in preventing symptomatic RSV infections in older adults.

KW - CD4+ T cell

KW - T-cell memory

KW - antibody function

KW - cell-mediated immunity

KW - correlate of protection

KW - interferon-gamma

KW - machine learning

KW - respiratory syncytial virus

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U2 - 10.3389/fimmu.2023.1260146

DO - 10.3389/fimmu.2023.1260146

M3 - Article

C2 - 37936699

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1260146

ER -

T cells, more than antibodies, may prevent symptoms developing from respiratory syncytial virus infections in older adults

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