title: H5N1 vaccine-specific B cell responses in ferrets primed with live attenuated seasonal influenza vaccines.
abstract: BACKGROUND
  Live attenuated influenza H5N1 vaccines have been produced and evaluated in mice and ferrets that were never exposed to influenza A virus infection (Suguitan et al., Plos Medicine, e360:1541, 2006). However, the preexisting influenza heterosubtypic immunity on live attenuated H5N1 vaccine induced immune response has not been evaluated.
  
  
  RESULTS
  Primary and recall B cell responses to live attenuated H5N1 vaccine viruses were examined using a sensitive antigen-specific B cell ELISpot assay to investigate the effect of preexisting heterosubtypic influenza immunity on the development of H5N1-specific B cell immune responses in ferrets. Live attenuated H5N1 A/Hong Kong/213/03 and A/Vietnam/1203/04 vaccine viruses induced measurable H5-specific IgM and IgG secreting B cells after intranasal vaccination. However, H5-specific IgG secreting cells were detected significantly earlier and at a greater frequency after H5N1 inoculation in ferrets previously primed with trivalent live attenuated influenza (H1N1, H3N2 and B) vaccine. Priming studies further revealed that the more rapid B cell responses to H5 resulted from cross-reactive B cell immunity to the hemagglutinin H1 protein. Moreover, vaccination with the H1N1 vaccine virus was able to induce protective responses capable of limiting replication of the H5N1 vaccine virus to a level comparable with prior vaccination with the H5N1 vaccine virus without affecting H5N1 vaccine virus induced antibody response.
  
  
  CONCLUSIONS
  The findings indicate that previous vaccination with seasonal influenza vaccine may accelerate onset of immunity by an H5N1 ca vaccine and the heterosubtypic immunity may be beneficial for pandemic preparedness.
authors.affiliation: MedImmune, Mountain View, California, United States of America.
authors.forename: Xing
authors.initials: X
authors.lastname: Cheng
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenbraun
authors.forename: Qi
authors.initials: Q
authors.lastname: Xu
authors.forename: Helen
authors.initials: H
authors.lastname: Zhou
authors.forename: Deepali
authors.initials: D
authors.lastname: Kulkarni
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
authors.forename: George
authors.initials: G
authors.lastname: Kemble
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D004797:Enzyme-Linked Immunosorbent Assay; D005289:Ferrets / Q000276:immunology* / Q000821:virology; D006388:Hemagglutinins / Q000276:immunology; D007109:Immunity; D007117:Immunization, Secondary; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology* / Q000502:physiology; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D012621:Seasons; D013045:Species Specificity; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology*; D014779:Virus Replication
chemical_list: D006388:Hemagglutinins; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated