title: Immunogenicity of virosomal adjuvanted trivalent influenza vaccination in allogeneic stem cell transplant recipients.
abstract: BACKGROUND
  Influenza vaccination is generally recommended to hematopoietic stem cell transplant (HSCT) recipients. However, the seasonal subunit vaccination response is frequently suboptimal, and alternate more efficient vaccination systems must be examined. We compared the immunogenicity of an adjuvanted virosomal influenza and subunit vaccine in HSCT recipients.
  
  
  METHODS
  The immunogenicity after a single dose (0.5 mL) of adjuvanted trivalent virosomal vaccination was evaluated in a study cohort of 21 HSCT recipients and compared to a control cohort of 30 HSCT recipients who received a single dose (0.5 mL) of non-adjuvanted seasonal trivalent subunit vaccination over 4 seasons from 2010 to 2014. Whole blood interferon-gamma (IFN-γ) release assays were tested, both before and 30 days after vaccination, in response to influenza pandemic (pdm) H1N1, H3N2, and B antigens. HLA-A*02 dextramers, to gauge for the absolute number of antigen-specific CD8(+) T-cells, and pdm 2009 hemagglutinin inhibition (HI) assays, to test for neutralizing antibodies, were used as immunological readouts.
  
  
  RESULTS
  The pdm HI titers were poor in both cohorts with only 23% (5/21) after virosomal vaccination and 13.3% (4/30) in the seasonal vaccine cohort having protective titers (≥40). The delta change of IFN-γ production in response to influenza pdm H1N1 (P = 0.005) and influenza B antigens (P = 0.01) were significantly elevated in blood from individuals who received the virosomal as compared to the seasonal vaccine. The IFN-γ response to pdm H1N1 was stronger (P < 0.001), as compared to seasonal vaccination, in patients vaccinated >6 month post HSCT. We detected a significant increase in the frequency of matrix 1 (GILGFVTL) dextramer-specific CD8(+) T-cells after the virosomal vaccine (P = 0.01). No differences were seen in the hemagglutinin-specific CD8(+) T-cells between the 2 cohorts.
  
  
  CONCLUSIONS
  Vaccination using a virosomal delivery system is beneficial in eliciting robust cellular immune responses to pdm H1N1 influenza in SCT recipients.
authors: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.|Department of Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: A
authors: A
authors: Ambati
authors: Sahlgrens University Hospital, Goteborg, Sweden.
authors: S
authors: S
authors: Einarsdottir
authors: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.|Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.
authors: I
authors: I
authors: Magalhaes
authors: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: T
authors: T
authors: Poiret
authors: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.
authors: R
authors: R
authors: Bodenstein
authors: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.|Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
authors: K
authors: K
authors: LeBlanc
authors: Sahlgrens University Hospital, Goteborg, Sweden.
authors: M
authors: M
authors: Brune
authors: Department of Laboratory Medicine, Karolinska Institutet, Huddinge, Sweden.|Center for Allogeneic Stem Cell Transplantation, Karolinska University Hospital, Stockholm, Sweden.
authors: M
authors: M
authors: Maeurer
authors: Department of Medicine, Karolinska Institutet, Huddinge, Sweden.|Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
authors: P
authors: P
authors: Ljungman
mesh_terms: D000277:Adjuvants, Pharmaceutic; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012621:Seasons; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013548:Sweden; D014184:Transplantation, Homologous / Q000009:adverse effects; D014611:Vaccination; D055815:Young Adult
chemical_list: D000277:Adjuvants, Pharmaceutic; D007252:Influenza Vaccines; D007371:Interferon-gamma
keywords: adjuvant; dextramers; inactivated; influenza vaccination; interferon-gamma; seasonal; subunit; transplantation; virosomal