Submitted to: Journal of Virology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/2/2005
Publication Date: 2/1/2006
Citation: Gao, W., Soloff, A.C., Lu, X., Montecalvo, A., Matsuoka, Y., Robbins, P.D., Swayne, D.E., Donis, R.O., Katz, J.M., Barratt-Boyes, S.M., Gambotto, A. 2006. Protective vaccine for the rapid response to lethal Avian Influenza outbreaks. Journal of Virology. 80:1959-1964. Interpretive Summary: The recent emergence of H5N1 deadly avian influenza (AI) strains in poultry and their transmission to and infection of humans in southeast Asia has raised concerns about another influenza pandemic. An adenoviral-vectored H5 influenza A vaccine was rapidly developed and evaluated. Using a mouse model, the vaccine provided protection from lethal intranasal challenge by a Vietnam H5N1 AI virus that had killed a person. A single injection of the vaccine under the skin of chickens protected them from a massive intranasal challenge by the same Vietnam H5N1 virus. The rapid development, production and administration adenovirus-vectored vaccines to birds and high-risk individuals may serve to control the pandemic spread of lethal avian influenza.
Technical Abstract: The recent emergence of highly pathogenic avian influenza (HPAI) strains in poultry and their subsequent transmission to humans in southeast Asia has raised concerns about the potential pandemic spread of lethal disease1,2. Here we describe the rapid development of an adenoviral-based influenza A vaccine directed against the hemagglutinin (HA) protein of the A/Vietnam/1203/2004 (H5N1) (VN/1203/04) strain isolated during the 2003-2005 lethal human outbreak in Vietnam. Vaccination of mice induced HA-specific neutralizing antibodies and broad cellular immunity likely to provide heterosubtypic immunity. Mice vaccinated with full-length HA were fully protected from a lethal intranasal challenge with VN/1203/04. Vaccination with the HA2 subunit induced robust cellular immunity but negligible humoral immunity and protected 60% of mice from lethal intranasal VN/1203/04 infection, suggesting a role for cellular immunity in control of influenza. A single subcutaneous immunization completely protected chickens from a massive intranasal challenge with VN/1203/04 capable of killing all control-vaccinated chickens within 2 days. The rapid production and administration of recombinant adenovirus-based vaccines to birds and high-risk individuals may serve to control the pandemic spread of lethal avian influenza.