title: Responses to A(H1N1)pdm09 influenza vaccines in participants previously vaccinated with seasonal influenza vaccine: a randomized, observer-blind, controlled study.
abstract: BACKGROUND
  Prior receipt of a trivalent seasonal influenza vaccine (TIV) can affect hemagglutination inhibition (HI) antibody responses to pandemic influenza vaccines. We investigated the effect of TIV priming on humoral responses to AS03-adjuvanted and nonadjuvanted A(H1N1)pdm09 vaccines, the role of AS03 on cell-mediated immune (CMI) responses, and vaccine safety.
  
  
  METHODS
  Healthy adults (aged 19-40 years) were randomized 1:1:1:1 to receive TIV or saline followed 4 months later by 2 doses, 3 weeks apart, of adjuvanted or nonadjuvanted A(H1N1)pdm09 vaccine and followed up to study end (day 507). Pre- and postvaccination responses of HI and neutralizing antibody, CD4(+)/CD8(+) T cells, memory B cells, and plasmablasts were assessed.
  
  
  RESULTS
  Ninety-nine of the 133 participants enrolled completed the study. No vaccine-related serious adverse events were recorded. In TIV-primed participants, A(H1N1)pdm09-specific antibody and CD4(+) T-cell and memory B-cell responses to the pandemic vaccine tended to be diminished. Vaccine adjuvantation led to increased responses of vaccine-homologous and -heterologous HI and neutralizing antibodies and CD4(+) T cells, homologous memory B cells, and plasmablasts.
  
  
  CONCLUSIONS
  In healthy adults, prior TIV administration decreased humoral and CMI responses to A(H1N1)pdm09 vaccine. Adjuvantation of A(H1N1)pdm09 antigen helped to overcome immune interference between the influenza vaccines. No safety concerns were observed.
  
  
  BACKGROUND
  Clinical Trials.gov identifier NCT00707967.
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Sumita
authors.initials: S
authors.lastname: Roy-Ghanta
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: Robbert
authors.initials: R
authors.lastname: Van der Most
authors.affiliation: GlaxoSmithKline Vaccines, King of Prussia, Pennsylvania.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: GlaxoSmithKline Vaccines, Rixensart, Belgium.
authors.forename: David W
authors.initials: DW
authors.lastname: Vaughn
mesh_terms: D000328:Adult; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D056724:Immunity, Humoral / Q000276:immunology; D007115:Immunization Schedule; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D016037:Single-Blind Method; D055815:Young Adult
chemical_list: C517981:FluLaval; D007252:Influenza Vaccines
keywords: A(H1N1)pdm09 vaccine; AS03; B cells; CD4+ T cells; HI antibody; TIV; immune interference; neutralizing antibody; pandemic influenza; plasmablasts