title: B-sides serologic markers of immunogenicity in kidney transplanted patients: report from 2012-2013 flu vaccination experience.
abstract: BACKGROUND
  Safety and immunogenicity data of seasonal influenza vaccination in transplanted patients (Tps) are controversial. Preexisting cross-reactive antibodies generated by repeated vaccination with drift variant strains could bias interpretation of immunogenicity data in Tp.
  
  
  METHODS
  The unadjuvanted 2012-2013 seasonal influenza vaccine was administered to 81 kidney Tps being routinely vaccinated against influenza and 23 healthy controls (HCs). Immunogenicity was evaluated by both strain-specific antibody responses with standard hemagglutination inhibition assay and by memory B-cell enzyme-linked immunosorbent spot. Safety was also evaluated by measuring anti-human leukocyte antigen (HLA) antibodies.
  
  
  RESULTS
  The majority of Tps were seroprotected before vaccination (81.5%, 81.5%, and 43.2% vs. 47.8%, 34.8%, and 30.4% in HC for H1N1, H3N2, and B strain, respectively) resulting into lower seroconversion rates (P≤0.01) as compared with HC (40.7%, 39.5%, and 54.3% vs. 73.9%, 82.6%, and 65.2% for H1N1, H3N2, and B strain, respectively). An inverse correlation was found between seroconversion rates and number of previous vaccinations in Tps. On the contrary, similar increase in the frequencies of strain-specific memory B cells were detected by B-cell enzyme-linked immunosorbent spot in both Tps and HCs after vaccination. No serious adverse events have been reported. Donor-specific HLA antibodies increased in two patients after vaccination, and de novo anti-HLA antibodies were identified in two additional patients (non-donor-specific HLA antibodies).
  
  
  CONCLUSIONS
  This report on safety and immunogenicity of the seasonal unadjuvanted 2012-2013 flu vaccination suggests that evaluating immunogenicity of influenza vaccination exclusively by hemagglutination inhibition assay may be misleading in individuals receiving yearly seasonal vaccines. Further investigations are required to understand the relation between vaccination and anti-HLA antibody development.
authors.affiliation: 1 Department of System Medicine, University of Rome, Tor Vergata, Rome, Italy. 2 University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, Rome, Italy. 3 WHO National Influenza Centre, Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy. 4 National Council of Researches IFT Unit of Rome S. Camillo Hospital, Regional Transplant Center Lazio (CRTL), S. Camillo Hospital, Rome, Italy. 5 Pediatric Medicine and Infectious Disease, Pediatrics Medicine Department, Bambino Gesù Children's Hospital, Roma, Italy. 6 Department of Nephrology and Urology, Bambino Gesù Children's Hospital, Rome, Italy. 7 Address correspondence to: Paolo Palma, M.D., Ph.D., University Department of Pediatrics, DPUO, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy and Luca Dello Strologo, M.D., Department of Nephrology and Urology, Bambino Gesù Children's Hospital, Piazza S. Onofrio 4, 00165 Rome, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Alberto
authors.initials: A
authors.lastname: Cagigi
authors.forename: Veronica
authors.initials: V
authors.lastname: Santilli
authors.forename: Federica
authors.initials: F
authors.lastname: Zotta
authors.forename: Angela
authors.initials: A
authors.lastname: di Martino
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Castrucci
authors.forename: Isabella
authors.initials: I
authors.lastname: Donatelli
authors.forename: Elvira
authors.initials: E
authors.lastname: Poggi
authors.forename: Antonina
authors.initials: A
authors.lastname: Piazza
authors.forename: Andrea
authors.initials: A
authors.lastname: Campana
authors.forename: Isabella
authors.initials: I
authors.lastname: Guzzo
authors.forename: Alberto
authors.initials: A
authors.lastname: Villani
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Luca
authors.initials: L
authors.lastname: Dello Strologo
authors.forename: Paolo
authors.initials: P
authors.lastname: Palma
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006680:HLA Antigens / Q000276:immunology; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007156:Immunologic Memory; D007252:Influenza Vaccines / Q000276:immunology*; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation; D008297:Male; D013997:Time Factors; D014611:Vaccination
chemical_list: D000914:Antibodies, Viral; D006680:HLA Antigens; D007252:Influenza Vaccines; D007518:Isoantibodies