title: Improving immunity to Haemophilus influenzae in children with chronic suppurative lung disease.
abstract: BACKGROUND
  Endobronchial infections related to non-typeable Haemophilus influenzae (NTHi) are common in children and adults with suppurative airway disease such as bronchiectasis and COPD. Impaired cell mediated immune responses to NTHi have been described in these patients. Currently there are no interventions known to correct the deficiency in cell mediated immune responses to NTHi. The aim of this study was to determine if receipt of a conjugate vaccine containing protein D from H. influenzae is associated with improvement in NTHi-specific cytokine responses in children with chronic suppurative lung disease.
  
  
  METHODS
  Blood mononuclear cells from 107 young children with chronic suppurative lung disease and 32 healthy control children were stimulated in vitro with NTHi. We compared the cytokine production of stimulated mononuclear cells from children who had received the pneumococcal H. influenzae protein D conjugate vaccine with cells from children who received pneumococcal vaccines without protein D. Protein D-specific IgG1 was quantified in plasma.
  
  
  RESULTS
  Children with chronic suppurative lung disease who received ≥ 3 doses of the protein D conjugate vaccine produced significantly more IFNγ than children who received the alternative vaccines without protein D (median 939 versus 338 pg/ml; p = 0.007). Importantly, the amount of IFNγ produced by those vaccinated with the conjugate vaccine approached the levels observed in cells from healthy children. The conjugate vaccine was also associated with small but significant increases in IL-13 (p < 0.001) and IL-5 (p = 0.007). Protein D-specific IgG1 levels correlated with the number of PHiD-CV doses (p = 0.02).
  
  
  CONCLUSIONS
  Vaccination with PHiD-CV is associated with improvements in NTHi-specific cell-mediated and humoral immune responses in children with chronic suppurative lung disease.
authors.affiliation: Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia. Electronic address: susan.pizzutto@menzies.edu.au.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Pizzutto
authors.affiliation: Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia; Queensland Lung Transplant Service, The Prince Charles Hospital, QLD, Australia; School of Medicine, The University of Queensland, QLD, Australia.
authors.forename: Stephanie T
authors.initials: ST
authors.lastname: Yerkovich
authors.affiliation: School of Medicine, The University of Queensland, QLD, Australia; Department of Respiratory Medicine, Princess Alexandra Hospital, QLD, Australia.
authors.forename: John W
authors.initials: JW
authors.lastname: Upham
authors.affiliation: Telethon Kids Institute, The University of Western Australia, WA, Australia.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Hales
authors.affiliation: Telethon Kids Institute, The University of Western Australia, WA, Australia.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Thomas
authors.affiliation: Division of Child Health, Menzies School of Health Research, Charles Darwin University, NT, Australia; Department of Respiratory Medicine, Queensland Children's Medical Research Institute, Royal Children's Hospital, QLD, Australia.
authors.forename: Anne B
authors.initials: AB
authors.lastname: Chang
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D001987:Bronchiectasis / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary; D007072:Immunoglobulin D / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D015848:Interleukin-5 / Q000096:biosynthesis / Q000276:immunology; D008074:Lipoproteins / Q000276:immunology*; D008171:Lung Diseases / Q000150:complications / Q000276:immunology*; D008297:Male; D015876:Northern Territory; D022242:Pneumococcal Vaccines / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D016207:Cytokines; D007072:Immunoglobulin D; D007074:Immunoglobulin G; D018793:Interleukin-13; D015848:Interleukin-5; D008074:Lipoproteins; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate; D007371:Interferon-gamma; C067989:glpQ protein, Haemophilus influenzae
keywords: Cell mediated immune response; Non-CF bronchiectasis; Non-typeable Haemophilus influenzae; Pneumococcal H. influenzae protein-D conjugate vaccine