New Vaccination Strategy May Protect Against Both Lethal 1918 and H5N1 Influenza Viruses

A new study suggests that vaccination with 1918 H1N1 influenza virus-like particles not only protected mice and ferrets against the lethal 1918 influenza virus, but also displayed cross-reactive immunity against the potentially pandemic H5N1 influenza virus. The researchers from the National Center for Immunization and Respiratory Diseases, Collaborating Centers for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia; and Novavax, Inc., Rockville, Maryland report their findings in the June 2009 issue of the Journal of Virology.

More than 220,000 hospitalizations and approximately 36,000 deaths are attributed to influenza A viruses each year. Since the first confirmed human cases of avian influenza in 1997, more than 400 additional human H5N1 infections have occurred of which an estimated 60 percent have been fatal. As new subtypes continue to emerge and the threat of a pandemic is at its highest in decades, researchers are pursuing vaccine strategies that can induce cross-reactive immunity against multiple strains of influenza viruses.

In prior research virus-like particle (VLP) vaccines have proven to be a promising new technology at preventing diseases in humans. VLPs resemble their live-virus counterparts and are readily processed by the immune system, however, they lack the RNA required for virus replication.

In this study researchers generated VLPs from the structural proteins of the 1918 H1N1 virus and compared their ability to protect mice and ferrets against a reconstructed 1918 virus and the highly pathogenic avian H5N1 virus that was isolated from a fatal human case. When immunized twice intranasally with H1N1 VLPs mice were highly protected against a lethal challenge with both the 1918 and H5N1 virus. In contrast, mice receiving two intramuscular immunizations of 1918 VLPs were only protected against the 1918 viral challenge. Mucosal vaccination with 1918 VLPs induced higher levels of cross-reactivity in mice and complete survival in ferrets challenged with a lethal dose of the H5N1 virus. Only a 50 percent survival rate was noted in intramuscularly immunized animals.

"These results suggest a strategy of VLP vaccination against a pandemic virus and one that stimulates heterotypic immunity against an influenza virus strain with threatening pandemic potential," say the researchers.