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

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.

Reversion of Somatic Mutations of the Respiratory Syncytial Virus–Specific Human Monoclonal Antibody Fab19 Reveal a Direct Relationship between Association Rate and Neutralizing Potency

“…10 mg/ml. Abs with such low potency likely would not contribute significantly to viral immunity (50,51).…”

Biological challenges and technological opportunities for respiratory syncytial virus vaccine development

“…While immune-complex deposition was documented in children from the original FI-RSV vaccine trial and in animal models (45), this phenomenon has not been associated with severe disease from maternally derived or passively acquired antibodies, and has not been associated with severe disease following reinfection with RSV. In addition, unlike other vaccine-enhanced disease syndromes, in which antibody-dependent enhancement of disease occurs through facilitated entry by Fc-mediated binding, this has been evaluated in RSV and does not appear to apply (53). This phenomenon is typically associated with pathogens that have distinct macrophage tropism, which RSV does not.…”

How Innate Immune Mechanisms Contribute to Antibody-Enhanced Viral Infections

“…Initially, one lead hypothesis was that FI-RSV pathology was an example of ADE, as in the bonnet monkey model, antibody increased virus infection of pulmonary macrophages (21,61). However, in vivo, pulmonary epithelial cells and not macrophages are prime targets of infection.…”