A Preventative Adenoviral-Based H5N1 Influenza Vaccine

性状（由申请方提供）：野生水禽是所有已知甲型流感病毒的天然宿主，是导致家禽中高致死性疾病零星暴发的病毒来源。自1997年以来，高致病性（HP）甲型禽流感H5 N1病毒在香港引起了一系列疫情，最近在其他9个亚洲国家爆发。随着人类暴露于H5 N1病毒和感染H5 N1病毒的持续增加，产生禽-人重组病毒的可能性也在增加，该病毒可在缺乏对H5 N1病毒的HA特异性免疫力的人群中有效传播。1997年，HPA 1 H5 N1在香港导致从家禽传播给人类，导致18人感染和6人死亡。在2003- 2005年期间，高致病性禽流感A（H5 N1）在几个亚洲国家（柬埔寨、中国、印度尼西亚、日本、老挝、韩国、泰国和越南、朝鲜）大规模爆发，导致泰国17例人间病例，越南27例，柬埔寨3例;有51例报告死亡。家庭聚集性H5 N1感染增加了H5 N1病毒人际传播的可能性。我们最近开发了一种基于腺病毒的流感疫苗，该疫苗编码在2003-2005年致命的人类疫情期间分离的A/Vietnam/1203/2004（H5 N1）毒株的血凝素（HA）抗原。接种疫苗的小鼠和鸡具有广泛的病毒特异性细胞和体液免疫，并完全免受致命的鼻内H5 N1攻击，而所有对照动物在几天内死亡。因此，将提出集中和综合的疫苗临床试验。

DESCRIPTION (provided by applicant): 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.