title: Correlates of immunity to respiratory syncytial virus (RSV) associated-hospitalization: establishment of minimum protective threshold levels of serum neutralizing antibodies.
abstract: OBJECTIVE
  To determine if respiratory syncytial virus (RSV) specific, serum antibody titers correlate with protection against RSV associated-hospitalization at all ages.
  
  
  METHODS
  Participants who were enrolled in a trial to determine the frequency of specific virus infections associated with hospitalization [J. Am. Med. Assoc. 283 (2000) 499] were included in our analysis if they were enrolled from July 1991 to June 1993, had a culture for virus isolation, and provided blood samples at hospitalization and 14-60 days later. RSV infection was defined by a positive culture and/or serology. Microneutralization, ELISA to the fusion (F) protein and Western blot were the serological assays that were used to determine correlates of immunity.
  
  
  RESULTS
  One hundred and seventy-five individuals, 1 month to 89 years old, out of 538 patients hospitalized with an acute respiratory infection met the criteria for analysis. RSV associated-hospitalization occurred in 11 (40.7%) of 27 infants (<1 year), 8 (38.1%) of 21 young children (1 to <5 years), and 15 (11.8%) of 127 children and adults (> or =5 years). At the time of hospitalization, geometric mean neutralizing antibody titers (log(2)) to RSV/A and RSV/B, and geometric mean binding antibody titer (log(2)) to F protein were significantly higher in patients with non-RSV associated-hospitalization compared to those with RSV associated-hospitalization (RSV/A: 7.9 versus 6.1, P<0.001; RSV/B: 9.4 versus 7.3, P<0.001; ELISA-F, 13.9 versus 12.6, P=0.01). For every 1 log(2) increase in titer of neutralizing antibodies to RSV/A and RSV/B, and binding antibody to F protein there was a significant increase in the likelihood of not having an RSV associated-hospitalization by 22.3, 25, and 24.4% respectively. A minimal protective threshold titer of > or =6.0 (odds ratio 3.5; 95% CI 1.4-9.1) and > or =8.0 log(2) (odds ratio 2.9; 95% CI 1.1-7.7) against RSV associated-hospitalization was established for neutralizing antibodies to RSV/A and RSV/B; a threshold titer could not be established for binding antibody to F protein.
  
  
  CONCLUSIONS
  Participants with naturally acquired serum neutralizing antibody levels at least equal to the minimal protective threshold titer were approximately three times more likely not to have an RSV associated-hospitalization. We speculate that achieving a minimal protective threshold antibody titer through active immunization will significantly reduce RSV associated-hospitalization among all ages.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Rm. 248E, One Baylor Plaza, Houston, TX, USA. ppiedra@bcm.tmc.edu
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Piedra
authors.forename: Alan M
authors.initials: AM
authors.lastname: Jewell
authors.forename: Stanley G
authors.initials: SG
authors.lastname: Cron
authors.forename: Robert L
authors.initials: RL
authors.lastname: Atmar
authors.forename: W Paul
authors.initials: WP
authors.lastname: Glezen
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000914:Antibodies, Viral / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D009297:Nasal Mucosa / Q000821:virology; D009500:Neutralization Tests; D010614:Pharynx / Q000821:virology; D018357:Respiratory Syncytial Virus Infections / Q000453:epidemiology* / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D000914:Antibodies, Viral