title: Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients.
abstract: BACKGROUND
  Responses to influenza vaccines are poorly characterized in immunocompromised patients. The goal of this study was to assess the efficacy of the AS03-adjuvanted influenza H1N1/A/09 vaccine in allogeneic hematopoietic stem cell transplant recipients.
  
  
  METHODS
  We enrolled 65 patients and 138 controls in an open prospective study. Controls received one dose and patients 2 doses of the AS03-adjuvanted influenza H1N1/A/09 vaccine at a 3-week interval. Geometric mean titers and seroprotection/seroconversion rates were determined by hemagglutination inhibition before and four weeks after the last immunization. Clinical and biological markers, including immunoglobulins, CD3+, CD4+, CD8+ and naïve CD4+ T-cell counts were assessed in all patients.
  
  
  RESULTS
  Baseline seroprotection rates were low in patients (6.6%) and controls (14.8%). After 2 doses, patients (n=57, 92.3%) achieved similar seroprotection rates (84% vs. 87%, P=0.65) and antibody titers (305 vs. 340, P=0.88) as controls (n=131, 93.9%) after one dose. In univariate analysis, transplant-to-vaccination interval less than 12 months, active graft-versus-host disease, immunosuppressive drugs, hemoglobin less than 12 g/L, lymphopenia less than 1 G/L, IgG less than 4 g/L, IgA less than 0.5 g/L, IgM less than 0.5 g/L and naive CD4+ T cells less than 150/μL were significantly associated with weaker responses. Multivariate analysis identified transplant-to-vaccination interval and active graft-versus-host disease as the most powerful negative predictors of antibody responses (P=0.04 and P=0.002, respectively). Vaccination was well tolerated in both cohorts.
  
  
  CONCLUSIONS
  In allogeneic hematopoietic stem cell transplant recipients, 2 doses of an adjuvanted influenza vaccine elicited comparable responses to a single dose in healthy individuals. However, vaccine responses remained poor in patients with ongoing graft-versus-host disease, supporting the need for additional strategies in this high-risk patient population. (ClinicalTrials.gov Identifier: NCT01022905).
authors.affiliation: University Hospitals of Geneva, Centre for Vaccinology and Neonatal Immunology, Department of Pathology-Immunology and Pediatrics, Medical Faculty, Geneva, Switzerland. bilal.mohty@hcuge.ch
authors.forename: Bilal
authors.initials: B
authors.lastname: Mohty
authors.forename: Michael
authors.initials: M
authors.lastname: Bel
authors.forename: Marija
authors.initials: M
authors.lastname: Vukicevic
authors.forename: Monika
authors.initials: M
authors.lastname: Nagy
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Levrat
authors.forename: Sara
authors.initials: S
authors.lastname: Meier
authors.forename: Stephane
authors.initials: S
authors.lastname: Grillet
authors.forename: Christophe
authors.initials: C
authors.lastname: Combescure
authors.forename: Laurent
authors.initials: L
authors.lastname: Kaiser
authors.forename: Yves
authors.initials: Y
authors.lastname: Chalandon
authors.forename: Jakob
authors.initials: J
authors.lastname: Passweg
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
authors.forename: Eddy
authors.initials: E
authors.lastname: Roosnek
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007114:Immunization; D016867:Immunocompromised Host; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000276:immunology; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines