title: Response to pneumococcal polysaccharide vaccination in patients with chronic and allergic aspergillosis.
abstract: BACKGROUND
  Pneumococcal infection causes significant morbidity in patients with underlying lung disease, and vaccination has been associated with reduced disease rates. Response to vaccination has not been studied in chronic lung conditions characterised by ongoing infection or inflammation like chronic pulmonary aspergillosis (CPA).
  
  
  METHODS
  In a prospective observational study, consecutive patients with CPA, allergic aspergillosis and bronchiectasis attending a national referral centre received pneumococcal 23-valent polysaccharide vaccine (PPV-23) and had pre- and post-vaccination antibody concentrations quantified as part of routine clinical care. Serotype-specific pneumococcal IgG antibodies were quantified for 12 serotypes using a multiplex microsphere assay. A protective response was defined as a level of >1.3μg/mL or a ≥ fourfold rise in concentration for ≥70% of serotypes, pre to post-vaccination. C-reactive protein, Immunoglobulins and mannose binding lectin (MBL) levels were measured and correlated to vaccine response.
  
  
  RESULTS
  A total of 318 patients were enrolled. In vaccine-naïve patients (n=127), the lowest pre-vaccination levels were seen with serotypes 1 and 4 and the highest with serotype 19A. A protective response post-vaccination was seen in 50% of patients. The poorest responses were observed with serotypes 1, 3 and 4. Levels of C-reactive protein did not affect efficacy. Profound MBL deficiency was found in 28.8%; there were no significant differences in response to vaccination in patients with or without MBL deficiency. Post-vaccination serotype-specific concentrations waned gradually, however they were still elevated compared to pre-vaccination after 2-5 years.
  
  
  CONCLUSIONS
  Patients with chronic and allergic aspergillosis exhibited a poor response to PPV-23 vaccination compared to healthy adults. An alternative vaccination strategy or delay of vaccination until their underlying condition is better controlled, e.g. after treatment with antifungals may result in better response.
authors.affiliation: The National Aspergillosis Centre, University Hospital of South Manchester, The University of Manchester, Manchester Academic Health Science Centre, Southmoor Road, M23 9LT Manchester, UK. Electronic address: chris.kosmidis@manchester.ac.uk.
authors.forename: Chris
authors.initials: C
authors.lastname: Kosmidis
authors.affiliation: The National Aspergillosis Centre, University Hospital of South Manchester, The University of Manchester, Manchester Academic Health Science Centre, Southmoor Road, M23 9LT Manchester, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Powell
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Medical Microbiology Partnership, PO Box 209, Clinical Sciences Building, Manchester Royal Infirmary, Manchester M13 9WZ, UK.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: University of Manchester, 1st Floor, Education & Research Centre, University Hospital of South Manchester, Wythenshawe Hospital, Southmoor Road, Manchester M23 9LT, UK.
authors.forename: Julie
authors.initials: J
authors.lastname: Morris
authors.affiliation: Department of Immunology, Salford Royal Hospitals NHS Trust, Hope Hospital, Clinical Sciences Building, Stott Lane, Salford M6 8HD, UK.
authors.forename: Hana
authors.initials: H
authors.lastname: Alachkar
authors.affiliation: The National Aspergillosis Centre, University Hospital of South Manchester, The University of Manchester, Manchester Academic Health Science Centre, Southmoor Road, M23 9LT Manchester, UK.
authors.forename: David W
authors.initials: DW
authors.lastname: Denning
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000276:immunology*; D002097:C-Reactive Protein / Q000032:analysis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood; D008875:Middle Aged; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D037601:Mannose-Binding Lectin; D022242:Pneumococcal Vaccines; D002097:C-Reactive Protein
keywords: Allergic bronchopulmonary aspergillosis; Chronic pulmonary aspergillosis; Pneumococcal vaccination; Response