title: Safety and immunogenicity of live attenuated influenza reassortant H5 vaccine (phase I-II clinical trials).
abstract: OBJECTIVE
  Our studies aimed to evaluate in clinical trials the safety and immunogenicity of an H5 live influenza vaccine candidate obtained using classical reassortment techniques from a low pathogenicity avian influenza (LPAI) A/Duck/Potsdam/1402-6/86(H5N2) virus and the cold-adapted (ca) donor strain A/Leningrad/134/17/57(H2N2).
  
  
  METHODS
  During Phase I-II clinical trials, volunteers received intranasally two doses of reassortant influenza vaccine strain A/17/Duck/Potsdam/86/92 (H5N2) 21 days apart. Clinical examination of all vaccinees was conducted 7 days post-vaccination. Serum antibody responses were measured by hemagglutination-inhibition and microneutralization and local antibodies were estimated using an enzyme-linked immunosorbent assay test.
  
  
  RESULTS
  The vaccine was safe and of low reactogenicity with no febrile reactions. After revaccination 47.1-54.8% of subjects showed > or =fourfold seroconversions of Hamagglutination inhibition (HAI) antibodies to the hemagglutinin (HA) antigen of the A/17/Duck/Potsdam/86/92 (H5N2) virus and 29.4-30.8% were seroconverted to the HA antigen of the reverse genetics reassortant A/Indonesia/05/2005 x PR8 IBCDC-RG (H5N1). Virus-neutralizing antibody levels in sera of volunteers were similar to those shown in HAI test. The virus-specific nasal IgA antibody response after two vaccine doses demonstrated significant increases of > or =fourfold rise SIgA antibodies (65%) geometrical mean titers (16.0) and a rise in SIgA antibodies (2.8) compared with one dose.
  
  
  CONCLUSIONS
  The live attenuated influenza vaccine candidate prepared using the LPAI A(H5N2) strain was well tolerated and elicited serum and local immune responses. There was evident cross-reactivity to the A(H5N1) strain in the HAI test.
authors.affiliation: Institute of Experimental Medicine, Russian Academy of Medical Sciences, Acad. Pavlov's Street, Saint Petersburg, Russia. vaccine@mail.ru
authors.forename: Larisa
authors.initials: L
authors.lastname: Rudenko
authors.forename: Julia
authors.initials: J
authors.lastname: Desheva
authors.forename: Sergey
authors.initials: S
authors.lastname: Korovkin
authors.forename: Alexander
authors.initials: A
authors.lastname: Mironov
authors.forename: Andrey
authors.initials: A
authors.lastname: Rekstin
authors.forename: Elena
authors.initials: E
authors.lastname: Grigorieva
authors.forename: Svetlana
authors.initials: S
authors.lastname: Donina
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gambaryan
authors.forename: Anton
authors.initials: A
authors.lastname: Katlinsky
mesh_terms: D000281:Administration, Intranasal; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000032:analysis; D053121:Influenza A Virus, H2N2 Subtype / Q000235:genetics; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D053125:Influenza A Virus, H5N2 Subtype / Q000235:genetics* / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control*; D009297:Nasal Mucosa / Q000276:immunology; D009500:Neutralization Tests; D016865:Reassortant Viruses / Q000235:genetics / Q000276:immunology*; D012426:Russia; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007070:Immunoglobulin A; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated