Difference in respiratory syncytial virus-specific Fc-mediated antibody effector functions between children and adults

Anke J Lakerveld, Anne T Gelderloos, Rutger M Schepp, Cornelis A M de Haan, Robert S van Binnendijk, Nynke Y Rots, Josine van Beek, Cécile A C M van Els, Puck B van Kasteren*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Respiratory syncytial virus (RSV) infections are a major cause of bronchiolitis and pneumonia in infants and older adults, for which there is no known correlate of protection. Increasing evidence suggests that Fc-mediated antibody effector functions have an important role, but little is known about the development, heterogeneity, and durability of these functional responses. In light of future vaccine strategies, a clear view of the immunological background and differences between various target populations is of crucial importance. In this study, we have assessed both quantitative and qualitative aspects of RSV-specific serum antibodies, including IgG/IgA levels, IgG subclasses, antibody-dependent complement deposition, cellular phagocytosis, and NK cell activation (ADNKA). Samples were collected cross-sectionally in different age groups (11-, 24-, and 46-month-old children, adults, and older adults; n = 31–35 per group) and longitudinally following natural RSV infection in (older) adults (2–36 months post-infection; n = 10). We found that serum of 24-month-old children induces significantly lower ADNKA than the serum of adults (P < 0.01), which is not explained by antibody levels. Furthermore, in (older) adults we observed boosting of antibody levels and functionality at 2–3 months after RSV infection, except for ADNKA. The strongest decrease was subsequently observed within the first 9 months, after which levels remained relatively stable up to three years post-infection. Together, these data provide a comprehensive overview of the functional landscape of RSV-specific serum antibodies in the human population, highlighting that while antibodies reach adult levels already at a young age, ADNKA requires more time to fully develop.

Original languageEnglish
Article numberuxad101
Pages (from-to)79-93
Number of pages15
JournalClinical and Experimental Immunology
Volume214
Issue number1
Early online date22 Aug 2023
DOIs
Publication statusPublished - Oct 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.

Funding

This work was funded by the Dutch Ministry of Health, Welfare, and Sport (VWS).

FundersFunder number
Ministerie van Volksgezondheid, Welzijn en Sport

    Keywords

    • anti-viral immunity
    • antibodies
    • complement
    • cytotoxicity
    • phagocytosis

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