Evaluation of the respiratory syncytial virus G-directed neutralizing antibody response in the human airway epithelial cell model

Virology. 2020 Nov:550:21-26. doi: 10.1016/j.virol.2020.08.006. Epub 2020 Aug 20.

Abstract

Human respiratory syncytial virus (RSV) is a major cause of serious respiratory tract infections in infants and the elderly. Recently it was shown that the RSV G glycoprotein mediates attachment to cells using CX3CR1 as a receptor, and that G-specific neutralizing antibodies can be detected using human airway epithelial (HAE) cell cultures. To investigate the contributions of G-specific antibodies to RSV neutralization, we performed HAE neutralization assays on sera from RSV G-immunized mice or RSV-infected infants. We confirmed that G-specific neutralization using serum from mice or humans could only be detected on HAE cultures. We also found that RSV G-specific antibodies in infants were either subgroup specific or cross-neutralizing. Altogether, our results suggest that G is an important target for generating neutralizing antibodies and would be beneficial to include in an RSV vaccine. Further, inclusion of G antigens from both RSV subgroups may enhance the vaccine cross protection potency.

Keywords: Cross-neutralization; G; HAE; Neutralization; RSV; Subgroup.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / biosynthesis*
  • Antibodies, Viral / biosynthesis*
  • Antigens, Viral / administration & dosage
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • CX3C Chemokine Receptor 1 / genetics
  • CX3C Chemokine Receptor 1 / immunology*
  • Chlorocebus aethiops
  • Epithelial Cells / immunology
  • Epithelial Cells / virology
  • Female
  • Gene Expression
  • Humans
  • Immune Sera / chemistry
  • Immunization
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological
  • Neutralization Tests
  • Protein Binding
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / virology
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / genetics
  • Respiratory Syncytial Virus, Human / immunology*
  • Respiratory Syncytial Virus, Human / pathogenicity
  • Vero Cells
  • Viral Fusion Proteins / administration & dosage
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / immunology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • CX3C Chemokine Receptor 1
  • CX3CR1 protein, human
  • Cx3cr1 protein, mouse
  • G glycoprotein, Respiratory syncytial virus
  • Immune Sera
  • Receptors, Virus
  • Viral Fusion Proteins