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Title: PATHOGENICITY AND IMMUNOGENICITY OF INFLUENZA VIRUSES WITH GENES FROM THE 1918 PANDEMIC VIRUS

Author
item Tumpey, Terrence
item GARCIA-SASTRE, ADOLFO - MT SINAI SCL OF MED-NY
item TAUBENBERGER, JEFFERY - ARMED FORCES INST. MD
item PALESE, PETER - MT SINAI SCL OF MED-NY
item Swayne, David

Submitted to: Proceedings of the National Academy of Sciences (PNAS)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/16/2003
Publication Date: 3/2/2004
Citation: Tumpey, T., Garcia-Sastre, A., Taubenberger, J.K., Palese, P., Swayne, D.E. 2004. Pathogenicity and immunogenicity of influenza viruses with genes from the 1918 pandemic virus. The National Academy of Sciences. 101(9):3166-3171.

Interpretive Summary: An H1N1 influenza virus caused the 1918 pandemic. Five genes were evaluated in a recombinant virus for the ability to cause disease in a mouse model. The presence of the 1918 viruses hemagglutinin and neuramindase genes killed the mice. Vaccination of the mice with the 1918 recombinant, or a 1930 pig influenza virus protected the mice from the 1918 influenza virus. Vaccines using newer strains of H1N1 influenza virus did not provide complete protection from the 1918 virus. This suggests effective vaccines can be developed against the 1918 virus should it re-emerge in the human population.

Technical Abstract: The 1918 influenza A H1N1 virus caused the worst pandemic of influenza ever recorded. To better understand the pathogenesis and immunity to the 1918 pandemic virus, we generated recombinant influenza viruses possessing two to five genes of the 1918 influenza virus. Recombinant influenza viruses possessing the hemagglutinin (HA), neuraminidase (NA), matrix (M), nonstructural (NS), and nucleoprotein (NP) genes or any recombinant virus possessing both the HA and NA genes of the 1918 influenza virus were highly lethal for mice. Antigenic analysis by hemagglutination inhibition (HI) tests with ferret and chicken H1N1 antisera demonstrated that the 1918 recombinant viruses antigenically most resembled A/Swine/Iowa/30 (Sw/Iowa/30) virus, but differed from H1N1 viruses isolated since 1930. HI and virus neutralizing (VN) antibodies to 1918 recombinant and Sw/Iowa/30 viruses in human sera were present among individuals born before or shortly after the 1918 pandemic. Mice that received an intramuscular immunization of the homologous or Sw/Iowa/30 inactivated vaccine developed HI and VN antibodies to the 1918 recombinant virus and were completely protected against lethal challenge. Mice that received A/PR/8/34, A/Texas/36/91 or A/New Caledonia/20/99 H1N1 vaccines displayed partial protection from lethal challenge. In contrast, control vaccinated mice were not protected against lethal challenge and displayed high virus titers in respiratory tissues. Partial vaccine protection mediated by baculovirus-expressed recombinant HA vaccines suggest common cross-reactive epitopes on the H1 HA. These data suggest a strategy of vaccination that would be effective against a re-emergent 1918 or 1918-like virus.