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Updated: Aug 11, 2026

An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection
Published on: December 10, 2013
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.
Abstract:
The neutralizing and enhancing activities of respiratory syncytial virus (RSV)-specific antibodies were examined. These two biological activities were measured for a panel of six monoclonal antibodies (MAbs) specific to the RSV surface F and G glycoproteins. Four MAbs specific for the F protein possessed both neutralizing and enhancing activities. One MAb (11-2-D2), specific to the G protein, enhanced RSV infection of U937 cells, a human macrophage cell line, but did not neutralize virus infectivity. One MAb (11-3-A3), specific to the F protein, efficiently neutralized virus infectivity but did not enhance RSV infection of U937 cells. MAb 11-3-A3 neutralized representative strains of the two antigenic subtypes of RSV. Assays performed with mixtures of MAbs showed that high concentrations of MAb 11-3-A3 masked the enhancing activity of MAb 11-2-D2. The assay of mixtures of two MAbs possessing only enhancing activities demonstrated that this response was synergistic. The role of neutralizing and enhancing antibodies in determining the outcome of RSV infection was examined for infants from whom cord blood serum samples were collected at birth. There was no significant difference in the magnitude of the serum-enhancing activities between infants who were hospitalized with RSV infections and a group of age- and sex-matched control infants with no reported respiratory illness requiring hospitalization. However, the results indicated a possible correlation between RSV infection of the infants and the occurrence of in vitro antibody-dependent enhancement of the cord blood sera at a serum dilution of 10(-2). A significant inverse correlation was found between the plaque-neutralizing and enhancing activities of the cord blood sera from infants, irrespective of subsequent RSV infection. These data are discussed in relation to the possible contribution of antibody-dependent enhancement to the normal course of RSV pathology in vivo.
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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