title: PHiD-CV induces anti-Protein D antibodies but does not augment pulmonary clearance of nontypeable Haemophilus influenzae in mice.
abstract: BACKGROUND
  A recently-licensed 10-valent pneumococcal conjugate vaccine (PHiD-CV; Synflorix, GSK) uses Protein D from Haemophilus influenzae as a carrier protein. PHiD-CV therefore has the potential to provide additional protection against nontypeable H. influenzae (NTHi). NTHi frequently causes respiratory tract infections and is associated with significant morbidity and mortality worldwide and there is currently no vaccine.
  
  
  METHODS
  We developed mouse models of NTHi infection and influenza/NTHi superinfection. Mice were immunized with PHiD-CV, heat-killed NTHi, or a 13-valent pneumococcal conjugate vaccine that did not contain Protein D (PCV13; Prevenar, Pfizer) and then infected intranasally with NTHi.
  
  
  RESULTS
  Infection with NTHi resulted in weight loss, inflammation and airway neutrophilia. In a superinfection model, prior infection with pandemic H1N1 influenza virus (strain A/England/195/2009) augmented NTHi infection severity, even with a lower bacterial challenge dose. Immunization with PHiD-CV produced high levels of antibodies that were specific against Protein D, but not heat-killed NTHi. Immunization with PHiD-CV led to a slight reduction in bacterial load, but no change in disease outcome.
  
  
  CONCLUSIONS
  PHiD-CV induced high levels of Protein D-specific antibodies, but did not augment pulmonary clearance of NTHi. We found no evidence to suggest that PHiD-CV will offer added benefit by preventing NTHi lung infection.
authors.affiliation: Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London W2 1PG, UK.
authors.forename: Matthew K
authors.initials: MK
authors.lastname: Siggins
authors.affiliation: Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London W2 1PG, UK.
authors.forename: Simren K
authors.initials: SK
authors.lastname: Gill
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Langford
authors.affiliation: Section of Paediatrics, Imperial College London, London W2 1PG, UK.
authors.forename: Yanwen
authors.initials: Y
authors.lastname: Li
authors.affiliation: Immunisation Department, Public Health England, Colindale, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group, St. George's University of London, SW17 0RE, UK.
authors.forename: Shamez N
authors.initials: SN
authors.lastname: Ladhani
authors.affiliation: Mucosal Infection & Immunity Group, Section of Virology, Imperial College London, St Mary's Campus, London W2 1PG, UK. Electronic address: john.tregoning@imperial.ac.uk.
authors.forename: John S
authors.initials: JS
authors.lastname: Tregoning
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000276:immunology*; D001835:Body Weight; D002352:Carrier Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006193:Haemophilus influenzae / Q000276:immunology*; D007072:Immunoglobulin D / Q000276:immunology*; D008074:Lipoproteins / Q000276:immunology*; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000150:complications; D022242:Pneumococcal Vaccines / Q000008:administration & dosage*; D018410:Pneumonia, Bacterial / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology; D015163:Superinfection / Q000276:immunology / Q000473:pathology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D002352:Carrier Proteins; D007072:Immunoglobulin D; D008074:Lipoproteins; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines; C067989:glpQ protein, Haemophilus influenzae
keywords: Antibody; Co-infection; Influenza; Innate immunity; Nontypeable Haemophilus influenzae; Pneumococcal conjugate vaccine; Pneumonia