title: Live attenuated H7N7 influenza vaccine primes for a vigorous antibody response to inactivated H7N7 influenza vaccine.
abstract: BACKGROUND
  H7 influenza viruses have emerged as potential pandemic threat. We evaluated the safety and immunogenicity of two candidate H7 pandemic live attenuated influenza vaccines (pLAIV) and their ability to prime for responses to an unadjuvanted H7 pandemic inactivated influenza vaccine (pIIV).
  
  
  METHODS
  Healthy seronegative adults received two doses of A/Netherlands/219/03 (H7N7) or one dose of A/chicken/British Columbia/CN-6/04 (H7N3) pLAIV all given as 10(7.5) 50% tissue culture infective doses (TCID50) intranasally. A subset of subjects received one 45 μg dose of H7N7 pIIV containing the A/Mallard/Netherlands/12/2000 HA intramuscularly 18-24 months after pLAIV. Viral shedding was assessed by culture and real-time polymerase chain reaction (rRT-PCR), B cell responses following pLAIV were evaluated by ELISPOT and flow cytometry. Serum antibody was assessed by hemagglutination-inhibition (HAI), microneutralization (MN) and ELISA assays after each vaccine.
  
  
  RESULTS
  Serum HAI or MN responses were not detected in any subject following one or two doses of either H7 pLAIV, although some subjects had detectable H7 specific B cells after vaccination. However, 10/13 subjects primed with two doses of H7N7 pLAIV responded to a subsequent dose of the homologous H7N7 pIIV with high titer HAI and MN antibody that cross-reacted with both North American and Eurasian lineage H7 viruses, including H7N9. In contrast, naïve subjects and recipients of a single dose of the mismatched H7N3 pLAIV did not develop HAI or MN antibody after pIIV.
  
  
  CONCLUSIONS
  While pLAIVs did not elicit detectable serum MN or HAI antibody, strain-specific pLAIV priming established long term immune memory that was cross-reactive with other H7 influenza strains. Understanding the mechanisms underlying priming by pLAIV may aid in pandemic vaccine development.
authors.affiliation: Division of Infectious Disease, University of Rochester Medical Center, Rochester, NY, United States.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Babu
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, United States.
authors.forename: Min
authors.initials: M
authors.lastname: Levine
authors.affiliation: Division of Infectious Disease, University of Rochester Medical Center, Rochester, NY, United States.
authors.forename: Theresa
authors.initials: T
authors.lastname: Fitzgerald
authors.affiliation: Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Catherine
authors.initials: C
authors.lastname: Luke
authors.affiliation: David Smith Center for Immunology and Vaccine Biology, University of Rochester Medical Center, Rochester, NY, United States.
authors.forename: Mark Y
authors.initials: MY
authors.lastname: Sangster
authors.affiliation: MedImmune LLC, Gaithersburg, MD, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Jin
authors.affiliation: David Smith Center for Immunology and Vaccine Biology, University of Rochester Medical Center, Rochester, NY, United States.
authors.forename: David
authors.initials: D
authors.lastname: Topham
authors.affiliation: Influenza Division, Centers for Disease Control and Prevention, Atlanta, GA, United States.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Katz
authors.affiliation: Division of Infectious Disease, University of Rochester Medical Center, Rochester, NY, United States. Electronic address: John_Treanor@urmc.rochester.edu.
authors.forename: John
authors.initials: J
authors.lastname: Treanor
authors.affiliation: Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
authors.forename: Kanta
authors.initials: K
authors.lastname: Subbarao
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D001402:B-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D057920:Influenza A Virus, H7N3 Subtype / Q000276:immunology; D053126:Influenza A Virus, H7N7 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control* / Q000821:virology; D009500:Neutralization Tests; D060888:Real-Time Polymerase Chain Reaction; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology; D014776:Virus Cultivation; D017201:Virus Shedding
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated
keywords: H7N7; Influenza; Live attenuated vaccine; Pandemic; Priming