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

Front Immunol. 2024 Oct 18:15:1448578. doi: 10.3389/fimmu.2024.1448578. eCollection 2024.

Abstract

Introduction: 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.

Methods: 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.

Results: 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 (>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.

Discussion: 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: RSV infections; humoral immunity; immune correlates; immune response; older adults; respiratory syncytial virus; symptomatic infections.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Neutralizing* / blood
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Viral* / blood
  • Antibodies, Viral* / immunology
  • Asymptomatic Infections
  • Europe / epidemiology
  • Female
  • Humans
  • Immunity, Mucosal
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Independent Living
  • Male
  • Middle Aged
  • Respiratory Syncytial Virus Infections* / diagnosis
  • Respiratory Syncytial Virus Infections* / epidemiology
  • Respiratory Syncytial Virus Infections* / immunology
  • Respiratory Syncytial Virus, Human* / immunology

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Antibodies, Neutralizing
  • Immunoglobulin A

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Respiratory Syncytial Virus Consortium in Europe (RESCEU) project. RESCEU has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (grant number 116019). This Joint Undertaking receives support from the European Union Horizon 2020 Research and Innovation.