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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Viral Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1448578

Serum and mucosal antibody-mediated protection and identification of asymptomatic respiratory syncytial virus infection in communitydwelling older adults in Europe

Provisionally accepted
Deniz Oner Deniz Oner 1Charlotte Vernhes Charlotte Vernhes 2Sunita Balla Sunita Balla 3Annick Moureau Annick Moureau 2*Marjolein Crabbe Marjolein Crabbe 1*Bruno Salaun Bruno Salaun 4Arangassery R. Bastian Arangassery R. Bastian 3*Kim Thys Kim Thys 1*Jonathan De Smedt Jonathan De Smedt 5*Salo Ooft Salo Ooft 3*Koos Korsten Koos Korsten 6,7Niels Adriaenssens Niels Adriaenssens 8,9*Samuel Coenen Samuel Coenen 8,9Christopher C. Butler Christopher C. Butler 10*Theo J. Verheij Theo J. Verheij 11*Simon Drysdale Simon Drysdale 12,13*Joanne G. Wildenbeest Joanne G. Wildenbeest 14*Andrew Pollard Andrew Pollard 12Peter J. Openshaw Peter J. Openshaw 15Louis Bont Louis Bont 6Jeroen Aerssens Jeroen Aerssens 1*
  • 1 Janssen Pharmaceutica NV, Beerse, Belgium
  • 2 Sanofi, Lyon, France
  • 3 Janssen Vaccines and Prevention, Pharmaceutical Companies of Johnson and Johnson, Leiden, Netherlands
  • 4 GlaxoSmithKline, Rixensart, Belgium
  • 5 GlaxoSmithKline (Belgium), Rixensart, Belgium
  • 6 Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children’s Hospital, Utrecht, Netherlands, Netherlands
  • 7 Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Center, Amsterdam, Netherlands
  • 8 Department of Primary and Interdisciplinary Care (ELIZA)-Centre for General Practice, University of Antwerp, Antwerp, Antwerp, Belgium
  • 9 Laboratory of Medical Microbiology, ​Vaccine and Infectious Disease Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Antwerp, Belgium
  • 10 Nuffield Department of Primary Health Care Health Sciences, Medical Sciences Division, University of Oxford, Oxford, England, United Kingdom
  • 11 Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands, Netherlands
  • 12 NIHR Oxford Biomedical Research Centre, Oxford Vaccine Group, Oxford, United Kingdom
  • 13 Centre for Neonatal and Paediatric Infection, Institute for Infection and Immunity, St George's, University of London, London, England, United Kingdom
  • 14 Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, Netherlands, Netherlands
  • 15 National Heart and Lung Institute, Faculty of Medicine, Imperial College London, London, England, United Kingdom

The final, formatted version of the article will be published soon.

    Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (> 60 years) with frailty and comorbidities. 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 (N=30), non-RSV (RSV negative) ARTI (N=386), and no ARTI (N=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. Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4-to-1.6-fold change (FC) for RSV-pre-and post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (> 80% and >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. 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.

    Keywords: respiratory syncytial virus1, RSV infections2, Older Adults3, immune correlates4, Immune response5, symptomatic infections6, humoral immunity7

    Received: 13 Jun 2024; Accepted: 17 Sep 2024.

    Copyright: © 2024 Oner, Vernhes, Balla, Moureau, Crabbe, Salaun, Bastian, Thys, De Smedt, Ooft, Korsten, Adriaenssens, Coenen, Butler, Verheij, Drysdale, Wildenbeest, Pollard, Openshaw, Bont and Aerssens. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Annick Moureau, Sanofi, Lyon, France
    Marjolein Crabbe, Janssen Pharmaceutica NV, Beerse, 2340, Belgium
    Arangassery R. Bastian, Janssen Vaccines and Prevention, Pharmaceutical Companies of Johnson and Johnson, Leiden, 2301, Netherlands
    Kim Thys, Janssen Pharmaceutica NV, Beerse, 2340, Belgium
    Jonathan De Smedt, GlaxoSmithKline (Belgium), Rixensart, 1330, Belgium
    Salo Ooft, Janssen Vaccines and Prevention, Pharmaceutical Companies of Johnson and Johnson, Leiden, 2301, Netherlands
    Niels Adriaenssens, Department of Primary and Interdisciplinary Care (ELIZA)-Centre for General Practice, University of Antwerp, Antwerp, 2000, Antwerp, Belgium
    Christopher C. Butler, Nuffield Department of Primary Health Care Health Sciences, Medical Sciences Division, University of Oxford, Oxford, OX2 6GG, England, United Kingdom
    Theo J. Verheij, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, 3584, Netherlands, Netherlands
    Simon Drysdale, NIHR Oxford Biomedical Research Centre, Oxford Vaccine Group, Oxford, United Kingdom
    Joanne G. Wildenbeest, Department of Paediatric Infectious Diseases and Immunology, Wilhelmina Children's Hospital, Utrecht, 3584, Netherlands, Netherlands
    Jeroen Aerssens, Janssen Pharmaceutica NV, Beerse, 2340, Belgium

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.