Influenza viruses are widely distributed in nature and can infect a wide variety of birds and mammals. In humans, seasonal influenza causes approximately 50,000 deaths yearly in the United States alone. In addition, global influenza pandemics have occurred when a new pathogenic influenza virus appears. The lack of immunity to the new influenza subtype means that large portions of the global population can be affected; the 1918 influenza pandemic is thought to have caused 40 – 50 million deaths worldwide.

Influenza viruses are classified on the basis of the antigenicity of their surface hemagglutinin glycoproteins (HA) and neuraminidase (NA). To date, 16 HA and 9 NA genes are known to exist. However, human influenza has been limited to only three HA (H1, H2, and H3) and two NA (N1 and N2) subtypes. The other HA and NA subtypes circulate in other avian and mammalian species. Until recently, the avian influenza viruses were not thought to pose a risk to humans. However, in 1997, 18 individuals in Hong Kong were infected with an avian influenza virus of the H5N1 subtype resulting in 6 deaths. Since then, the highly pathogenic H5N1 influenza virus has spread in wild bird populations, caused significant outbreaks in domestic poultry and continues to infect humans due to bird contact.

Since 2003, H5N1 avian influenza has infected 281 individuals leading to 169 deaths. Should the virus mutate or reassort so that it can be transmitted from human to human as effectively as the current seasonal influenza viruses, the global case load and mortality could be staggering.

The most effective means of reducing the spread and the clinical consequences of influenza is by vaccination. The principle behind the generation of human influenza vaccines is to elicit protective antibodies directed primarily against HA, the major protective antigen of the virus that induces neutralizing antibodies. In the US, two types of vaccines are currently approved for human use; 1) inactivated virus, and 2) cold-adapted attenuated virus. Current influenza virus vaccines consist of 3 components: an H1N1, an H3N2 influenza A virus, and an influenza B virus. Changes in the HA of circulating viruses (antigenic drift) require periodic replacement of the vaccine strains during inter-pandemic periods. The inactivated virus vaccines are manufactured in eggs and have an efficacy in the range of 50-80%, depending on the recipient’s age and health status. Current research efforts to improve the efficacy of influenza vaccines include the use of adjuvants and/or novel delivery methods that could significatly augment the levels and duration of the immune responses.

Inviragen will engineer the safe poxvirus vector, MVA, to express avian influenza antigens using the principles the Company has developed in its plague vaccine program. The Company’s goal is to develop a recombinant viral avian influenza vaccine that will be intranasally administered, provide rapid protection from infection, and provide cross-protection against different H5N1 viruses. A grant to support this research is in administrative review at NIAID; the Company expects the grant to be funded and our research to initiate in the second quarter of 2007.

More Avian Influenza Facts.

Centers for Disease Control and Prevention:
http://www.cdc.gov/flu/avian//

World Health Organization:
http://www.who.int/csr/disease/avian_influenza/en/