Characterization of an influenza A H5N2 reassortant as a candidate for live-attenuated and inactivated vaccines against highly pathogenic H5N1 viruses with pandemic potential

Vaccine. 2006 Nov 17;24(47-48):6859-66. doi: 10.1016/j.vaccine.2006.06.023. Epub 2006 Jun 28.

Abstract

We generated a high-growth 7:1 reassortant (Len17/H5) that contained the hemagglutinin (HA) gene from non-pathogenic A/Duck/Potsdam/1402-6/86 (H5N2) virus and other genes from the cold-adapted (ca) attenuated A/Leningrad/134/17/57 (H2H2) strain. Len17/H5 demonstrated an attenuated phenotype in mice and did not infect chickens. Mice administered Len17/H5 either as a live-attenuated intranasal vaccine or as an inactivated intramuscular vaccine were substantially protected from lethal challenge with highly pathogenic A/Hong Kong/483/97 (H5N1) virus and were protected from pulmonary infection with antigenically distinct A/Hong Kong/213/2003 (H5N1) virus. The cross-protective effect correlated with the levels of virus-specific mucosal IgA and/or serum IgG antibodies. Our results suggest a new strategy of using classical genetic reassortment between a high-growth ca H2N2 strain and antigenically related non-pathogenic avian viruses to prepare live-attenuated and inactivated vaccines for influenza pandemic.

MeSH terms

  • Animals
  • Antibodies, Viral / biosynthesis
  • Antibodies, Viral / immunology
  • Chickens / immunology*
  • Cross Reactions
  • Disease Outbreaks
  • Female
  • Humans
  • Immunization
  • Influenza A Virus, H5N1 Subtype / immunology*
  • Influenza A Virus, H5N1 Subtype / pathogenicity
  • Influenza A Virus, H5N2 Subtype / immunology*
  • Influenza Vaccines / immunology*
  • Influenza in Birds / immunology*
  • Influenza in Birds / prevention & control*
  • Influenza, Human / immunology*
  • Influenza, Human / prevention & control*
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / virology
  • Vaccines, Attenuated / immunology
  • Vaccines, Inactivated / immunology
  • Virus Replication

Substances

  • Antibodies, Viral
  • Influenza Vaccines
  • Vaccines, Attenuated
  • Vaccines, Inactivated