title: Distinct patterns of B-cell activation and priming by natural influenza virus infection versus inactivated influenza vaccination.
abstract: BACKGROUND
  The human B-cell response to natural influenza virus infection has not been extensively investigated at the polyclonal level.
  
  
  METHODS
  The overall B-cell response of patients acutely infected with the 2009 pandemic influenza A(H1N1)pdm09 virus (A[H1N1]pdm09) was analyzed by determining the reactivity of plasmablast-derived polyclonal antibodies (PPAbs) to influenza proteins. Recipients of inactivated influenza vaccine containing the same A(H1N1)pdm09 strain were studied for comparison.
  
  
  RESULTS
  During acute infection, robust plasmablast responses to the infecting virus were detected, characterized by a greater PPAb reactivity to the conserved influenza virus nuclear protein and to heterovariant and heterosubtypic hemagglutinins, in comparison to responses to the inactivated A(H1N1)pdm09 vaccine. In A(H1N1)pdm09 vaccinees, the presence of baseline serum neutralizing antibodies against A(H1N1)pdm09, suggesting previous exposure to natural A(H1N1)pdm09 infection, did not affect the plasmablast response to vaccination, whereas repeated immunization with inactivated A(H1N1)pdm09 vaccine resulted in significantly reduced vaccine-specific and cross-reactive PPAb responses.
  
  
  CONCLUSIONS
  Natural A(H1N1)pdm09 infection and inactivated A(H1N1)pdm09 vaccination result in very distinct patterns of B-cell activation and priming. These differences are likely to be associated with differences in protective immunity, especially cross-protection against heterovariant and heterosubtypic influenza virus strains.
authors.affiliation: Department of Medicine VA Palo Alto Health Care System, California.
authors.forename: Xiao-Song
authors.initials: XS
authors.lastname: He
authors.affiliation: Department of Psychiatry and Behavioral Sciences.
authors.forename: Tyson H
authors.initials: TH
authors.lastname: Holmes
authors.affiliation: Department of Medicine VA Palo Alto Health Care System, California.
authors.forename: Mrinmoy
authors.initials: M
authors.lastname: Sanyal
authors.affiliation: Department of Microbiology, Global Health and Emerging Pathogens Institute.
authors.forename: Randy A
authors.initials: RA
authors.lastname: Albrecht
authors.affiliation: Department of Microbiology, Global Health and Emerging Pathogens Institute Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.affiliation: Department of Pediatrics.
authors.forename: Cornelia L
authors.initials: CL
authors.lastname: Dekker
authors.affiliation: Department of Microbiology and Immunology Institute for Immunity, Transplantation, and Infection Howard Hughes Medical Institute, Stanford University School of Medicine.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
authors.affiliation: Department of Medicine Department of Microbiology and Immunology VA Palo Alto Health Care System, California.
authors.forename: Harry B
authors.initials: HB
authors.lastname: Greenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology*; D056738:Cross Protection; D003429:Cross Reactions; D005260:Female; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D014611:Vaccination; D015164:Vaccines, Inactivated; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D015164:Vaccines, Inactivated
keywords: B-cell response; antibody; influenza vaccine; influenza virus infection; plasmablast