AUTHOR=Öner Deniz , Vernhes Charlotte , Balla-Jhagjhoorsingh Sunita , Moureau Annick , Crabbe Marjolein , Salaun Bruno , Bastian Arangassery Rosemary , Thys Kim , De Smedt Jonathan , Ooft Salo N. , Korsten Koos , Adriaenssens Niels , Coenen Samuel , Butler Christopher C. , Verheij Theo J. M. , Drysdale Simon B. , Wildenbeest Joanne G. , Pollard Andrew J. , Openshaw Peter J. M. , Bont Louis , Aerssens Jeroen 

TITLE=Serum and mucosal antibody-mediated protection and identification of asymptomatic respiratory syncytial virus infection in community-dwelling older adults in Europe

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1448578

DOI=10.3389/fimmu.2024.1448578

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p>Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (&gt;60 years) with frailty and comorbidities.</p></sec><sec><title>Methods</title><p>To investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -post-fusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (<italic>N</italic> = 30), non-RSV (RSV negative) ARTI (<italic>N</italic> = 386), and no ARTI (<italic>N</italic> = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study.</p></sec><sec><title>Results</title><p>Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (&gt;80% and &gt;90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms.</p></sec><sec><title>Discussion</title><p>This study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a data-driven approach.</p></sec>