title: Attenuation of live respiratory syncytial virus vaccines is associated with reductions in levels of nasal cytokines.
abstract: BACKGROUND
  Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract illness (LRTI) in children. Several promising live-attenuated RSV vaccines are in development. Defining additional markers of attenuation could enhance clinical trials.
  
  
  METHODS
  We used clinical data, virologic data, and nasal wash (NW) specimens from 20 RSV-naive children enrolled in studies of 4 live-attenuated RSV vaccines. Seven received minimally attenuated cpts248/955 or cpts530/1009 (group 1), 6 received moderately attenuated cpts248/404 (group 2), and 7 received highly attenuated rA2cp248/404/1030/ΔSH (group 3). NW specimens were tested for cytokines and chemokines via an electrochemiluminescence biosensor assay.
  
  
  RESULTS
  Group 1 exhibited 1 instance of LRTI and significantly higher rates of fever than groups 2 or 3; there were no significant differences in peak titers of vaccine virus in NW specimens. In contrast, levels of interferon γ, interleukin 1β, interleukin 2, interleukin 6, and interleukin 13 were significantly greater in NW specimens from group 1, compared with those from group 3. Maximum increases in levels of most cytokines occurred after peak viral replication but coincided with clinical illness.
  
  
  CONCLUSIONS
  Substantial increases in proinflammatory, antiinflammatory, T-helper 1, T-helper 2, and regulatory cytokines were detected in children who received minimally attenuated live RSV vaccines but not in children who received highly attenuated vaccines. Levels of cytokines in NW specimens may be useful biomarkers of attenuation for live RSV vaccines.
authors.affiliation: Center for Immunization Research, Department of International Health, Johns Hopkins Bloomberg School of Public HealthBaltimore, Maryland, USA. rkarron@jhsph.edu
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
authors.forename: Bhagvanji
authors.initials: B
authors.lastname: Thumar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Schappell
authors.forename: Ursula J
authors.initials: UJ
authors.lastname: Buchholz
authors.forename: Peter L
authors.initials: PL
authors.lastname: Collins
mesh_terms: D015374:Biosensing Techniques; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007223:Infant; D008163:Luminescent Measurements; D008297:Male; D009297:Nasal Mucosa / Q000737:chemistry / Q000276:immunology*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000472:pathogenicity; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D016207:Cytokines; D022261:Respiratory Syncytial Virus Vaccines; D014613:Vaccines, Attenuated