title: A live attenuated influenza A(H5N1) vaccine induces long-term immunity in the absence of a primary antibody response.
abstract: BACKGROUND
  Highly pathogenic avian influenza A(H5N1) causes severe infections in humans. We generated 2 influenza A(H5N1) live attenuated influenza vaccines for pandemic use (pLAIVs), but they failed to elicit a primary immune response. Our objective was to determine whether the vaccines primed or established long-lasting immunity that could be detected by administration of inactivated subvirion influenza A(H5N1) vaccine (ISIV).
  
  
  METHODS
  The following groups were invited to participate in the study: persons who previously received influenza A(H5N1) pLAIV; persons who previously received an irrelevant influenza A(H7N3) pLAIV; and community members who were naive to influenza A(H5N1) and LAIV. LAIV-experienced subjects received a single 45-μg dose of influenza A(H5N1) ISIV. Influenza A(H5N1)- and LAIV-naive subjects received either 1 or 2 doses of ISIV.
  
  
  RESULTS
  In subjects who had previously received antigenically matched influenza A(H5N1) pLAIV followed by 1 dose of ISIV compared with those who were naive to influenza A(H5N1) and LAIV and received 2 doses of ISIV, we observed an increased frequency of antibody response (82% vs 50%, by the hemagglutination inhibition assay) and a significantly higher antibody titer (112 vs 76; P = .04). The affinity of antibody and breadth of cross-clade neutralization was also enhanced in influenza A(H5N1) pLAIV-primed subjects.
  
  
  CONCLUSIONS
  ISIV administration unmasked long-lasting immunity in influenza A(H5N1) pLAIV recipients, with a rapid, high-titer, high-quality antibody response that was broadly cross-reactive across several influenza A(H5N1) clades.
  
  
  BACKGROUND
  NCT01109329.
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Kawsar R
authors.initials: KR
authors.lastname: Talaat
authors.affiliation: Laboratory of Infectious Diseases.
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Luke
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
authors.forename: Surender
authors.initials: S
authors.lastname: Khurana
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
authors.forename: Jody
authors.initials: J
authors.lastname: Manischewitz
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
authors.forename: Lisa R
authors.initials: LR
authors.lastname: King
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Bridget A
authors.initials: BA
authors.lastname: McMahon
authors.affiliation: Center For Immunization Research, Johns Hopkins Bloomberg School of Public Health, Baltimore.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Karron
authors.affiliation: PATH, Seattle, Washington.
authors.forename: Kristen D C
authors.initials: KD
authors.lastname: Lewis
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
authors.forename: Jing
authors.initials: J
authors.lastname: Qin
authors.affiliation: Biostatistics Research Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Follmann
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland.
authors.forename: Hana
authors.initials: H
authors.lastname: Golding
authors.affiliation: PATH, Seattle, Washington.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Neuzil
authors.affiliation: Laboratory of Infectious Diseases.
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D000915:Antibody Affinity; D000917:Antibody Formation / Q000276:immunology; D003429:Cross Reactions; D005260:Female; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D057920:Influenza A Virus, H7N3 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000276:immunology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated
keywords: H5N1; avian influenza; live attenuated; vaccine