Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation

Elisabeth A van Erp; Anke J Lakerveld; Erik de Graaf; Mads D Larsen; Rutger M Schepp; Agnes L Hipgrave Ederveen; Inge Ml Ahout; Cornelis Am de Haan; Manfred Wuhrer; Willem Luytjes; Gerben Ferwerda; Gestur Vidarsson; Puck B van Kasteren

doi:10.1002/cti2.1112

Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation

Clin Transl Immunology. 2020 Feb 19;9(2):e1112. doi: 10.1002/cti2.1112. eCollection 2020.

Authors

Elisabeth A van Erp^{1

2

3}, Anke J Lakerveld¹, Erik de Graaf⁴, Mads D Larsen⁴, Rutger M Schepp¹, Agnes L Hipgrave Ederveen⁵, Inge Ml Ahout^{2

3}, Cornelis Am de Haan⁶, Manfred Wuhrer⁵, Willem Luytjes¹, Gerben Ferwerda^{2

3}, Gestur Vidarsson⁴, Puck B van Kasteren¹

Affiliations

¹ Centre for Infectious Disease Control National Institute for Public Health and the Environment (RIVM) Bilthoven The Netherlands.
² Section Pediatric Infectious Diseases Laboratory of Medical Immunology Radboud Institute for Molecular Life Sciences, Radboudumc Nijmegen The Netherlands.
³ Radboud Center for Infectious Diseases, Radboudumc Nijmegen The Netherlands.
⁴ Department of Experimental Immunohematology Sanquin Research and Landsteiner Laboratory Amsterdam University Medical Center, University of Amsterdam Amsterdam The Netherlands.
⁵ Center for Proteomics and Metabolomics Leiden University Medical Center Leiden The Netherlands.
⁶ Department of Infectious Diseases and Immunology Virology Division Faculty of Veterinary Medicine Utrecht University Utrecht The Netherlands.

Abstract

Objectives: Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants, and there is no vaccine available. In early life, the most important contributors to protection against infectious diseases are the innate immune response and maternal antibodies. However, antibody-mediated protection against RSV disease is incompletely understood, as both antibody levels and neutralisation capacity correlate poorly with protection. Since antibodies also mediate natural killer (NK) cell activation, we investigated whether this functionality correlates with RSV disease.

Methods: We performed an observational case-control study including infants hospitalised for RSV infection, hernia surgery or RSV-negative respiratory viral infections. We determined RSV antigen-specific antibody levels in plasma using a multiplex immunoassay. Subsequently, we measured the capacity of these antibodies to activate NK cells. Finally, we assessed Fc-glycosylation of the RSV-specific antibodies by mass spectrometry.

Results: We found that RSV-specific maternal antibodies activate NK cells in vitro. While concentrations of RSV-specific antibodies did not differ between cases and controls, antibodies from infants hospitalised for severe respiratory infections (RSV and/or other) induced significantly less NK cell interferon-γ production than those from uninfected controls. Furthermore, NK cell activation correlated with Fc-fucosylation of RSV-specific antibodies, but their glycosylation status did not significantly differ between cases and controls.

Conclusion: Our results suggest that Fc-dependent antibody function and quality, exemplified by NK cell activation and glycosylation, contribute to protection against severe RSV disease and warrant further studies to evaluate the potential of using these properties to evaluate and improve the efficacy of novel vaccines.

Keywords: Fc‐mediated effector functions; NK cell; antibody‐dependent cell‐mediated cytotoxicity; fucosylation; interferon‐gamma; respiratory syncytial virus.