title: Responses of solid organ transplant recipients to the AS03-adjuvanted pandemic influenza vaccine.
abstract: BACKGROUND
  Solid organ transplant (SOT) recipients are a priority group for influenza vaccination and strategies enhancing immunogenicity are needed.
  
  
  METHODS
  We determined adverse reactions, changes in biomarkers of graft function and immune responses to two doses of the AS03-adjuvanted influenza A/09/H1N1 vaccine in 216 SOT recipients and in 138 controls after one dose. Antibody responses were measured by haemagglutination inhibition and confirmed by microneutralization. We calculated geometric mean titres (GMT) and seroprotection rates (GMT≥40).
  
  
  RESULTS
  Adverse reactions were fewer than in controls and graft function remained unaffected. Seroprotection was achieved by only 70.3% of SOT recipients, with significant differences between groups (lung 43.6%, heart 72.0%, kidney 83.3%, liver 83.3% and pancreas 85%), compared to 87% of controls (P<0.001). The weakest responses (seroprotection 43.5%) were elicited in lung transplant recipients. GMT remained threefold lower (115 versus 340) in SOT recipients than controls. Multivariate analyses identified increasing age, type of transplant and increasing blood levels of mycophenolate as independently associated to weaker responses. In contrast, even high blood levels of calcineurin inhibitors remained without significant influence on vaccine responses.
  
  
  CONCLUSIONS
  The squalene-based adjuvanted A/09/H1N1 vaccine was safe in SOT recipients. However, even two doses of this adjuvanted influenza vaccine did not provide adequate protection for lung transplant recipients and those with high mycophenolate blood levels. Additional prophylactic measures should, therefore, be considered for these high-risk groups.
authors.affiliation: Center for Vaccinology, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.forename: Michael
authors.initials: M
authors.lastname: Bel
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Karine
authors.initials: K
authors.lastname: Hadaya
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Martin
authors.forename: Paola M
authors.initials: PM
authors.lastname: Soccal
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.forename: Stephane
authors.initials: S
authors.lastname: Noble
authors.forename: Sara
authors.initials: S
authors.lastname: Meier
authors.forename: Klara
authors.initials: K
authors.lastname: Posfay-Barbe
authors.forename: Stephane
authors.initials: S
authors.lastname: Grillet
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D013185:Squalene / Q000276:immunology; D055815:Young Adult
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007166:Immunosuppressive Agents; D007252:Influenza Vaccines; D013185:Squalene