TY - JOUR
T1 - Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation
AU - van Erp, Elisabeth A.
AU - Lakerveld, Anke J.
AU - de Graaf, Erik
AU - Larsen, Mads D.
AU - Schepp, Rutger M.
AU - Hipgrave Ederveen, Agnes L.
AU - Ahout, Inge M. L.
AU - de Haan, Cornelis A. M.
AU - Wuhrer, Manfred
AU - Luytjes, Willem
AU - Ferwerda, Gerben
AU - Vidarsson, Gestur
AU - van Kasteren, Puck B.
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - Fc-mediated effector functions
KW - NK cell
KW - antibody-dependent cell-mediated cytotoxicity
KW - fucosylation
KW - interferon-gamma
KW - respiratory syncytial virus
UR - http://www.scopus.com/inward/record.url?scp=85082388081&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/cti2.1112
DO - https://doi.org/10.1002/cti2.1112
M3 - Article
C2 - 32099650
SN - 2050-0068
VL - 9
JO - Clinical & translational immunology
JF - Clinical & translational immunology
IS - 2
M1 - e1112
ER -