title: Assessment of human immune responses to H7 avian influenza virus of pandemic potential: results from a placebo-controlled, randomized double-blind phase I study of live attenuated H7N3 influenza vaccine.
abstract: BACKGROUND
  Live attenuated influenza vaccines (LAIVs) are being developed to protect humans against future epidemics and pandemics. This study describes the results of a double-blinded randomized placebo-controlled phase I clinical trial of cold-adapted and temperature sensitive H7N3 live attenuated influenza vaccine candidate in healthy seronegative adults.
  
  
  OBJECTIVE
  The goal of the study was to evaluate the safety, tolerability, immunogenicity and potential shedding and transmission of H7N3 LAIV against H7 avian influenza virus of pandemic potential.
  
  
  RESULTS
  Two doses of H7N3 LAIV or placebo were administered to 40 randomly divided subjects (30 received vaccine and 10 placebo). The presence of influenza A virus RNA in nasal swabs was detected in 60.0% and 51.7% of subjects after the first and second vaccination, respectively. In addition, vaccine virus was not detected among placebo recipients demonstrating the absence of person-to-person transmission. The H7N3 live attenuated influenza vaccine demonstrated a good safety profile and was well tolerated. The two-dose immunization resulted in measurable serum and local antibody production and in generation of antigen-specific CD4⁺ and CD8⁺ memory T cells. Composite analysis of the immune response which included hemagglutinin inhibition assay, microneutralization tests, and measures of IgG and IgA and virus-specific T cells showed that the majority (86.2%) of vaccine recipients developed serum and/or local antibodies responses and generated CD4⁺ and CD8⁺ memory T cells.
  
  
  CONCLUSIONS
  The H7N3 LAIV was safe and well tolerated, immunogenic in healthy seronegative adults and elicited production of antibodies broadly reactive against the newly emerged H7N9 avian influenza virus.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01511419.
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Rudenko
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Kiseleva
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Anatoly N
authors.initials: AN
authors.lastname: Naykhin
authors.affiliation: Department of Epidemiology and Prophylaxis, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Marianna
authors.initials: M
authors.lastname: Erofeeva
authors.affiliation: Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Marina
authors.initials: M
authors.lastname: Stukova
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Donina
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Petukhova
authors.affiliation: Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Pisareva
authors.affiliation: Department of Biotechnology, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Vera
authors.initials: V
authors.lastname: Krivitskaya
authors.affiliation: Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Michael
authors.initials: M
authors.lastname: Grudinin
authors.affiliation: Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Zhanna
authors.initials: Z
authors.lastname: Buzitskaya
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Isakova-Sivak
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Kuznetsova
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Natalie
authors.initials: N
authors.lastname: Larionova
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Julia
authors.initials: J
authors.lastname: Desheva
authors.affiliation: Department of Virology, Institute of Experimental Medicine, Saint Petersburg, Russia.
authors.forename: Irina
authors.initials: I
authors.lastname: Dubrovina
authors.affiliation: Department of Preclinical Trials, Microgen, Moscow, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nikiforova
authors.affiliation: Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.
authors.forename: John C
authors.initials: JC
authors.lastname: Victor
authors.affiliation: Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.
authors.forename: Kathy
authors.initials: K
authors.lastname: Neuzil
authors.affiliation: Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.
authors.forename: Jorge
authors.initials: J
authors.lastname: Flores
authors.affiliation: Program for Appropriate Technologies in Health, Seattle, Washington, United States of America.
authors.forename: Vadim
authors.initials: V
authors.lastname: Tsvetnitsky
authors.affiliation: Department of Molecular Virology, Institute of Influenza, Saint Petersburg, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Kiselev
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003080:Cold Temperature; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D057920:Influenza A Virus, H7N3 Subtype; D064766:Influenza A Virus, H7N9 Subtype; D007252:Influenza Vaccines / Q000276:immunology* / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D014613:Vaccines, Attenuated / Q000276:immunology / Q000627:therapeutic use; D014779:Virus Replication; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated