title: Comparative safety, immunogenicity, and efficacy of several anti-H5N1 influenza experimental vaccines in a mouse and chicken models (Testing of killed and live H5 vaccine).
abstract: OBJECTIVE
  Parallel testing of inactivated (split and whole virion) and live vaccine was conducted to compare the immunogenicity and protective efficacy against homologous and heterosubtypic challenge by H5N1 highly pathogenic avian influenza virus.
  
  
  METHODS
  Four experimental live vaccines based on two H5N1 influenza virus strains were tested; two of them had hemagglutinin (HA) of A/Vietnam/1203/04 strain lacking the polybasic HA cleavage site, and two others had hemagglutinins from attenuated H5N1 virus A/Chicken/Kurgan/3/05, with amino acid substitutions of Asp54/Asn and Lys222/Thr in HA1 and Val48/Ile and Lys131/Thr in HA2 while maintaining the polybasic HA cleavage site. The neuraminidase and non-glycoprotein genes of the experimental live vaccines were from H2N2 cold-adapted master strain A/Leningrad/134/17/57 (VN-Len and Ku-Len) or from the apathogenic H6N2 virus A/Gull/Moscow/3100/2006 (VN-Gull and Ku-Gull). Inactivated H5N1 and H1N1 and live H1N1 vaccine were used for comparison. All vaccines were applied in a single dose. Safety, immunogenicity, and protectivity against the challenge with HPAI H5N1 virus A/Chicken/Kurgan/3/05 were estimated.
  
  
  RESULTS
  All experimental live H5 vaccines tested were apathogenic as determined by weight loss and conferred more than 90% protection against lethal challenge with A/Chicken/Kurgan/3/05 infection. Inactivated H1N1 vaccine in mice offered no protection against challenge with H5N1 virus, while live cold-adapted H1N1 vaccine reduced the mortality near to zero level.
  
  
  CONCLUSIONS
  The high yield, safety, and protectivity of VN-Len and Ku-Len made them promising strains for the production of inactivated and live vaccines against H5N1 viruses.
authors.affiliation: M P Chumakov Institute of Poliomyelitis and Viral Encephalitides, RAMS, Moscow, Russia. alexandra.gambaryan@gmail.com
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Gambaryan
authors.forename: Natalia F
authors.initials: NF
authors.lastname: Lomakina
authors.forename: Elizaveta Y
authors.initials: EY
authors.lastname: Boravleva
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Kropotkina
authors.forename: Vadim V
authors.initials: VV
authors.lastname: Mashin
authors.forename: Igor V
authors.initials: IV
authors.lastname: Krasilnikov
authors.forename: Alexander I
authors.initials: AI
authors.lastname: Klimov
authors.forename: Larisa G
authors.initials: LG
authors.lastname: Rudenko
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D002645:Chickens; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D005585:Influenza in Birds / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D014613:Vaccines, Attenuated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D014613:Vaccines, Attenuated; D015164:Vaccines, Inactivated