Neutralizing and enhancing activities of human respiratory syncytial virus-specific antibodies

H B Gimenez1, S Chisholm, J Dornan

  • 1Department of Molecular and Cell Biology, University of Aberdeen, Marischal College, Scotland.

Insights

Respiratory syncytial virus (RSV) antibodies can neutralize or enhance infection. Some antibodies targeting the F protein neutralize, while G protein antibodies enhance, impacting RSV pathology.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Respiratory syncytial virus (RSV) is a major cause of respiratory illness in infants and young children.
  • Antibodies play a critical role in controlling viral infections, but their functions can be complex.
  • Both neutralizing and enhancing antibody activities against RSV have been observed, with implications for disease pathogenesis.

Purpose of the Study:

  • To investigate the neutralizing and enhancing activities of monoclonal antibodies (MAbs) against RSV surface glycoproteins (F and G).
  • To explore the relationship between these antibody activities and the outcome of RSV infection in infants.

Main Methods:

  • Characterization of six MAbs specific to RSV F and G proteins for neutralizing and enhancing activities.
  • In vitro assays using U937 cells (human macrophage cell line) to measure RSV infection enhancement.
  • Analysis of cord blood serum samples from infants with and without RSV infection to assess antibody activities.
  • Correlation analysis between neutralizing and enhancing antibody activities and clinical outcomes.

Main Results:

  • Four MAbs against the F protein exhibited both neutralizing and enhancing activities.
  • One G protein MAb (11-2-D2) enhanced infection but did not neutralize, while one F protein MAb (11-3-A3) neutralized but did not enhance.
  • Synergistic enhancing activity was observed with mixtures of enhancing MAbs.
  • No significant difference in serum-enhancing activity was found between hospitalized infants and controls, but a possible correlation with in vitro antibody-dependent enhancement (ADE) was noted.
  • A significant inverse correlation existed between neutralizing and enhancing activities in infant cord blood sera.

Conclusions:

  • Antibodies targeting RSV F and G glycoproteins have distinct neutralizing and enhancing properties.
  • Antibody-dependent enhancement (ADE) may contribute to RSV pathology in vivo.
  • The balance between neutralizing and enhancing antibodies is crucial in determining RSV infection outcomes.

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