Wild waterfowl, the natural hosts of all known influenza A viruses, are the source of viruses which cause sporadic outbreaks of highly fatal disease in domestic poultry. Since 1997, highly pathogenic (HP) avian influenza A H5N1 viruses have caused a series of outbreaks in Hong Kong, and most recently in 9 other Asian countries. As human exposure to and infection with H5N1 viruses continues to increase, so too does the likelihood of the generation of an avian-human reassortant virus which may transmit efficiently within the human population which lacks HA-specific immunity to H5N1 viruses. In 1997, HPAl H5N1 in Hong Kong resulted in transmission from poultry to humans, resulting in 18 infected people and six deaths. In 2003- 2005, extensive outbreaks of highly pathogenic avian influenza A (H5N1) occurred in several Asian countries (Cambodia, China, Indonesia, Japan, Laos, South Korea, Thailand and Vietnam, North Korea), resulting in 17 human cases in Thailand and 27 in Vietnam and 3 in Cambodia; there were 51 reported deaths. H5N1 infections in family clusters have raised the possibility of human-to-human transmission of H5N1 virus. We have recently developed an adenoviral-based influenza vaccine encoding the hemagglutinin (HA) antigen of the A/Vietnam/1203/2004 (H5N1) strain isolated during the 2003-2005 lethal human outbreak. Vaccinated mice and chickens had broad virus-specific cellular and humoral immunity and were fully protected from a lethal intranasal H5N1 challenge, whereas all control animals died within few days. Hence, a centralized and integrated clinical vaccine testing will be proposed. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI069282-02
Application #
7266987
Study Section
Vaccines Against Microbial Diseases (VMD)
Program Officer
Cho, David
Project Start
2006-08-01
Project End
2010-07-31
Budget Start
2007-08-01
Budget End
2010-07-31
Support Year
2
Fiscal Year
2007
Total Cost
$243,601
Indirect Cost
Name
University of Pittsburgh
Department
Surgery
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Steitz, Julia; Wagner, Robert A; Bristol, Tyler et al. (2010) Assessment of route of administration and dose escalation for an adenovirus-based influenza A Virus (H5N1) vaccine in chickens. Clin Vaccine Immunol 17:1467-72
Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D et al. (2008) Human infection with highly pathogenic H5N1 influenza virus. Lancet 371:1464-75