A Preventative Adenoviral-Based H5N1 Influenza Vaccine

基于腺病毒的预防性 H5N1 流感疫苗

• 批准号: 7266987
• 负责人: ANDREA GAMBOTTO
• 金额: $ 24.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7266987
• 关键词: Adenovirus Vector; Adenoviruses; Adult; Animal Model; Antigens; Asians; Avian Influenza; Awareness; Biological Products; Birds; Cambodia; Certification; Cessation of life; Chickens; China; Clinical; Clinical Research; Clinical Trials; Control Animal; Country; Cyclic GMP; Detection; Development; Disease; Disease Outbreaks; Domestic Fowls; Dose; Enrollment; Ensure; Evaluation; Exposure to; Family; Ferrets; Fever; Future; Generations; Goals; Hemagglutinin; Hong Kong; Human; Humoral Immunities; Immunity; Indonesia; Infection; Inflammation; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A virus; Injection of therapeutic agent; Japan; Laos; Liver; Manufactured Materials; Measures; Modeling; Mus; North Korea; Performance; Personal Satisfaction; Pharmacology; Pharmacology and Toxicology; Phase; Phase I Clinical Trials; Placebo Control; Population; Randomized; Reassortant Viruses; Recombinants; Registries; Reporting; Research; Research Personnel; Residual state; Safety; Saliva; Series; Serotyping; Site; Source; South Korea; T-Lymphocyte; Testing; Thailand; Thrombocytopenia; Toxic effect; United States; Universities; Urine; Vaccinated; Vaccination; Vaccine Research; Vaccines; Vietnam; Viral; Viral Genome; Viral Vector; Virus; base; cohort; day; exposed human population; healthy volunteer; immunogenicity; influenza virus vaccine; irritation; pandemic disease; pre-clinical; programs; research study; response; transmission process; vaccine evaluation; vector; Adenovirus Vector; Adenoviruses; Adult; Animal Model; Antigens; Asians; Avian Influenza; Awareness; Biological Products; Birds; Cambodia; Certification; Cessation of life; Chickens; China; Clinical; Clinical Research; Clinical Trials; Control Animal; Country; Cyclic GMP; Detection; Development; Disease; Disease Outbreaks; Domestic Fowls; Dose; Enrollment; Ensure; Evaluation; Exposure to; Family; Ferrets; Fever; Future; Generations; Goals; Hemagglutinin; Hong Kong; Human; Humoral Immunities; Immunity; Indonesia; Infection; Inflammation; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A virus; Injection of therapeutic agent; Japan; Laos; Liver; Manufactured Materials; Measures; Modeling; Mus; North Korea; Performance; Personal Satisfaction; Pharmacology; Pharmacology and Toxicology; Phase; Phase I Clinical Trials; Placebo Control; Population; Randomized; Reassortant Viruses; Recombinants; Registries; Reporting; Research; Research Personnel; Residual state; Safety; Saliva; Series; Serotyping; Site; Source; South Korea; T-Lymphocyte; Testing; Thailand; Thrombocytopenia; Toxic effect; United States; Universities; Urine; Vaccinated; Vaccination; Vaccine Research; Vaccines; Vietnam; Viral; Viral Genome; Viral Vector; Virus; base; cohort; day; exposed human population; healthy volunteer; immunogenicity; influenza virus vaccine; irritation; pandemic disease; pre-clinical; programs; research study; response; transmission process; vaccine evaluation; vector

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.

描述（由申请人提供）：野生水禽是所有已知流感病毒的天然宿主，是导致家禽中高度致命疾病的零星爆发的病毒来源。自1997年以来，高度致病的（HP）禽流感A H5N1病毒在香港以及最近在其他9个亚洲国家引起了一系列爆发。随着人类对H5N1病毒感染和感染的感染不断增加，因此产生禽类人类重新分类病毒的可能性也可能在人群中有效地传播，该病毒可能在人群中有效地传播，而该病毒缺乏对H5N1病毒的特异性免疫。 1997年，香港的HPAL H5N1导致从家禽传播到人类，导致18人受感染者和6例死亡。 2003年至2005年，在亚洲几个国家（柬埔寨，中国，印尼，日本，日本，老挝，韩国，泰国，泰国和越南，北朝鲜）发生了广泛的致病性禽流感（H5N1）的广泛爆发，在泰国和3个人类案例中，越南和3例在柬埔寨;报告了51例死亡。家庭簇中的H5N1感染提高了H5N1病毒的人类对人类传播的可能性。我们最近开发了一种基于腺病毒的流感疫苗，该疫苗编码了A/越南/1203/2004（H5N1）抗原的血凝素（HA）抗原，在2003-2005致命的人类暴发期间分离出来。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力，并受到全面保护的鼻内H5N1挑战，而所有对照动物都在几天内死亡。因此，将提出一种集中和集成的临床疫苗测试。