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

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

Deniz Öner  1 , Charlotte Vernhes  2 , Sunita Balla-Jhagjhoorsingh  3 , Annick Moureau  2 , Marjolein Crabbe  1 , Bruno Salaun  4 , Arangassery Rosemary Bastian  3 , Kim Thys  1 , Jonathan De Smedt  4 , Salo N Ooft  3 , Koos Korsten  5   6 , Niels Adriaenssens  7   8 , Samuel Coenen  7   8 , Christopher C Butler  9 , Theo J M Verheij  10 , Simon B Drysdale  11   12 , Joanne G Wildenbeest  5 , Andrew J Pollard  11 , Peter J M Openshaw  13 , Louis Bont  5 , Jeroen Aerssens  1
Affiliations

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

Deniz Öner et al. Front Immunol. .

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.

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Conflict of interest statement

DÖ, SB-J, MC, AB, KT, SO, and JA were employed at the time the work was performed by Janssen Pharmaceuticals, a Johnson & Johnson company, and may be Johnson & Johnson stockholders. CV and AM were employed by Sanofi at the time the work was performed and may be Sanofi stockholder. CV is now employed by Vaccines Europe, Brussels, Belgium. BS and JD are employed by GlaxoSmithKline and may be GlaxoSmithKline stockholders. CB has participated in two virtual Advisory Boards for Moderna relevant to RSV vaccination on 30 March 2023 and 18 May 2023 and received payments. TV has received grant from Innovative Medicines Initiative European Commission, in which Biomerieux, Abbott, BD, BioRad, Janssen contributed ValueDx project, NIHR for project on cellulitis, and NHS UK regional funding for project on respiratory tract infections. He have been on the Advisory Board of a US study on lower respiratory tract infections in primary care EAST-PC funded by the Agency for Healthcare Research and Quality. He is a member of the Dutch Health Council. SD has provided consultancy and/or investigator roles in relation to product development for Janssen, AstraZeneca, Pfizer, Moderna, Valneva, MSD, iLiAD and Sanofi with fees paid to St George’s, University of London. SD has been on the RSV advisory board Sanofi Pasteur and received fees. SD also received support for travel for chairing a conference session, fees paid to his institution SGUL. SD is a member of the UK Department of Health and Social Care’s DHSC Joint Committee on Vaccination and Immunisation JCVI RSV subcommittee and Medicines and Healthcare products Regulatory Agency’s MHRA Paediatric Medicine Expert Advisory Group PMEAG. JW is investigator for clinical trials funded by pharmaceutical companies including AstraZeneca, Merck, Pfizer, Sanofi, and Janssen and investigator for clinical trials funded by IMI/Horizon2020 and ZonMw, with payments paid to her institution. She was a speaker at Sanofi sponsored symposium ESPID, payments paid to her institution. JW participated in the advisory board of Janssen RSV older adults and Sanofi advisory board with fees paid to UMCU. AP is part of EC IMI Programme RESCEU, payments paid to his institution. He has received grants from Gates, Wellcome, CEPI, MRC, NIHR, Serum Institute of India, AstraZeneca, and EC, with payments paid to his institution. Oxford University has entered into a partnership with AZ for development of COVID-19 vaccines. AP is a contributor to intellectual property licensed by Oxford University Innovation to AstraZeneca. AP is chair of the UK Department of Health and Social Care’s DHSC Joint Committee on Vaccination and Immunisation JCVI, NIHR Senior Investigator, member of the Academy of Medical Sciences AMS and was a member of WHO’s SAGE until January 2022. AP’s institution received funding from the European Commission’s IMI programme for the conduct of this study. Oxford University has entered a partnership with AstraZeneca for the development of COVID-19 vaccines. PO received honoraria GSK, Pfizer Inc, Sanofi Pasteur, Seqirus, Moderna and Janssen for participation in advisory boards and expert meetings and for acting as a speaker in congresses outside the scope of the submitted work. PO is also a principal investigator in the INFLAMMAGE trial co-funded by the Medical Research Council UK and GSK as part of the EMINENT consortium to promote inflammation research. He received grants from UKRI-MRC/DHSC NIHR Grant award MR/V027859/1, and UKRI-BEIS for human infection challenge with SARS-CoV-2 and had roles as school governor Sidcot, Somerset. LB has regular interaction with pharmaceutical and other industrial partners. He has not received personal fees or other personal benefits. UMCU has received major funding >€100,000 per industrial partner for investigator-initiated studies from AbbVie, MedImmune, AstraZeneca, Sanofi, Janssen, Pfizer, MSD and MeMed Diagnostics. UMCU has received major funding for the RSV GOLD study from the Bill and Melinda Gates Foundation. UMCU has received major funding as part of the public private partnership IMI-funded RESCEU and PROMISE projects with partners GSK, Novavax, Janssen, AstraZeneca, Pfizer and Sanofi. UMCU has received major funding from Julius Clinical for participating in clinical studies sponsored by MedImmune and Pfizer. UMCU received minor funding €1,000-25,000 per industrial partner for consultation and invited lectures by AbbVie, MedImmune, Ablynx, Bavaria Nordic, MabXience, GSK, Novavax, Pfizer, Moderna, AstraZeneca, MSD, Sanofi, Genzyme, Janssen. LB is the founding chairman of the ReSViNET Foundation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the study design. (A) A total of 1,040 older adults were recruited before the start of two consecutive (2017–2019) RSV seasons (1 October to 1 May) and followed up during one season. In case of any ARTI, an RSV POCT RSV test was performed (results confirmed by qPCR). Mucosal (i.e., nasal swabs) and/or serum samples were collected at pre-RSV-season, RSV ARTI, and end-of-season visits. (B) After the exclusion of missing samples and participants with missed or delayed test, pre-RSV-season antibody levels of 754 participants were investigated for (symptomatic and asymptomatic) RSV ARTI compared with controls. ARTI, acute respiratory tract infection; N, number of participants; POCT, point-of-care test; PCR, polymerase chain reaction. Created with Biorender.com.
Figure 2
Figure 2
Correlates of protection of serum and mucosal antibodies. Forest plots showing the result of logistic regression analysis for the association of serum and mucosal antibodies with the probability of protection, or conversely symptomatic ARTI due to RSV. Arrows were colored for the following comparison groups. Green with square symbol for no ARTI (N = 338) versus RSV ARTI (N = 30), orange with triangle symbol for non-RSV (other) ARTI (N = 386) versus RSV ARTI (N = 30) in serum RSV-pre-F and -post-F binding IgG antibodies, blue with triangle symbol for a mixed group of controls (N = 119) versus RSV ARTI (N = 30) for the test in serum G binding IgG antibodies, and pink with triangle symbol for a subset group of controls (N = 45) versus RSV ARTI (N = 25) for the mucosal antibodies. Mean odds ratios (ORs) are reported for serum RSV-pre-F and -post-F binding IgG and neutralizing antibodies. Square or triangle dots for comparison of no ARTI versus RSV ARTI and other or subset group of other non-RSV ARTI versus RSV ARTI, respectively, represent the odds ratio, and the bars correspond to the confidence intervals (CIs) from 5% to 95%. Odds ratios and p-values were computed using the Fisher test described in the R glm package. *** represents a p-value < 0.001, ** represents a p-value < 0.01, and * represents a p-value < 0.05. ARTI, acute respiratory tract infection.
Figure 3
Figure 3
Antibody fold change (FC) over the season of study participants stratified by respiratory infection groups. (A) Box plots show the FC of RSV-pre-F and -post-F binding IgG and RSV-A2 neutralizing antibodies. The Y-axis shows log2 fold change of antibodies of participants stratified by their infection group based on molecular tests (POCT PCR and/or qPCR) and participants’ symptoms diary. Red dashed line shows log2 4 FC (=2). (B) Longitudinal analysis of RSV-pre-F and -post-F binding IgG antibodies and RSV-A2 neutralizing IgG antibody titers at pre-RSV-season, RSV, and end-of-season visits, stratified by respiratory infection status based on molecular tests and participants’ symptoms diary. Seroconversion is defined as having any antibody titer FC over the season above four. Participants with a positive seroconversion in any of the antibody titers were shown in dark blue and solid line. Participants with a negative seroconversion in any of the antibody titers were shown in gray and dashed line. Fold change (FC): ratio of end-of-season versus pre-RSV-season visit antibody levels. ARTI, acute respiratory tract infection; POCT, point-of-care test; PCR, polymerase chain reaction.
Figure 4
Figure 4
Identification of RSV asymptomatic participants through the receiver operating characteristic (ROC) curve method for RSV-pre-F and -post-F binding IgG, and RSV-A2 neutralizing Ig antibodies. (A–C) Log2-transformed FC of RSV ARTI (in blue) and controls were mapped. Black vertical dashed line shows the newly identified threshold for (A) RSV-pre-F binding IgG, (B) RSV-post-F binding IgG, and (C) RSV-A2 neutralizing IgG antibody assay. (D) Forest plots showing the result of logistic regression analysis for the association of serum antibodies with the probability of protection or infection for asymptomatic RSV. Square dots represent the odds ratio, and the bars correspond to the confidence intervals (CI) from 5% to 95%. Odds ratios and p-values were computed using the Fisher test described in the R glm package. * Represents a p-value < 0.05.
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References

    1. CDC . Learn about RSV in older adults with chronic medical conditions, in: Centers for Disease Control and Prevention (2022). Available online at: https://www.cdc.gov/rsv/high-risk/older-adults.html (Accessed January 9, 2023).
    1. Falsey AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high-risk adults. N Engl J Med. (2005) 352:1749–59. doi: 10.1056/NEJMoa043951 - DOI - PubMed
    1. Tseng HF, Sy LS, Ackerson B, Solano Z, Slezak J, Luo Y, et al. . Severe morbidity and short- and mid- to long-term mortality in older adults hospitalized with respiratory syncytial virus infection. J Infect Dis. (2020) 222:1298–310. doi: 10.1093/infdis/jiaa361 - DOI - PubMed
    1. Shi T, Denouel A, Tietjen AK, Campbell I, Moran E, Li X, et al. . Global disease burden estimates of respiratory syncytial virus–associated acute respiratory infection in older adults in 2015: A systematic review and meta-analysis. J Infect Dis. (2020) 222:S577–83. doi: 10.1093/infdis/jiz059 - DOI - PubMed
    1. Korsten K, Adriaenssens N, Coenen S, Butler C, Ravanfar B, Rutter H, et al. . Burden of respiratory syncytial virus infection in community-dwelling older adults in Europe (RESCEU): an international prospective cohort study. Eur Respir J. (2021) 57:2002688. doi: 10.1183/13993003.02688-2020 - DOI - PubMed

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