Antigenic Fingerprinting of Respiratory Syncytial Virus (RSV)-A-Infected Hematopoietic Cell Transplant Recipients Reveals Importance of Mucosal Anti-RSV G Antibodies in Control of RSV Infection in Humans

J Infect Dis. 2020 Feb 3;221(4):636-646. doi: 10.1093/infdis/jiz608.

Abstract

Background: Respiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplant (HCT) recipients. However, antibody responses that correlate with recovery from RSV disease are not fully understood.

Methods: In this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A-infected HCT recipients who recovered early (<14 days of RSV shedding) were compared with late-recovered patients (≥14 days of shedding) using gene fragment phage display libraries and surface plasmon resonance.

Results: Anti-F serum responses were similar between these 2 groups for antibody repertoires, neutralization titers, anti-F binding antibodies (prefusion and postfusion proteins), antibody avidity, and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV G antibody repertoires in the 2 groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain. Most importantly, a significantly higher antibody affinity to RSV G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT recipients.

Conclusions: These findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.

Keywords: HCT; RSV; antibody; antibody affinity; epitope; immune response; infection; mucosal immunity; repertoire; virus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood*
  • Antibody Affinity
  • Antigens, Viral / immunology*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin Idiotypes / immunology
  • Respiratory Mucosa / immunology*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / virology
  • Respiratory Syncytial Virus, Human / immunology*
  • Transplant Recipients*
  • Viral Envelope Proteins / immunology*
  • Viral Fusion Proteins / immunology
  • Virus Shedding

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Immunoglobulin G
  • Immunoglobulin Idiotypes
  • Viral Envelope Proteins
  • Viral Fusion Proteins
  • attachment protein G