Clinical Studies of Vaccines for Pandemic Influenza

大流行性流感疫苗的临床研究

• 批准号: 7592348
• 负责人: Kanta Subbarao
• 金额: $ 118.13万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592348
• 关键词: Adult; Affect; Africa; Amino Acids; Antibodies; Asia; Attenuated; Attenuated Live Virus Vaccine; Avian Influenza A Virus; Birds; British Columbia; Cessation of life; Chickens; Clinical; Clinical Research; Clinical Trials; Country; Data; Data Analyses; Disease; Disease Outbreaks; Domestic Fowls; Dose; Epidemic; Equilibrium; Europe; Ferrets; Genes; Goals; Hemagglutinin; Human; Immune response; Infection; Influenza; Influenza A Virus, H5N1 Subtype; Influenza A virus; Licensing; Life; Membrane Glycoproteins; Mus; Neuraminidase; Patients; Phase I Clinical Trials; Population; Range; Readiness; Reporting; Safety; Serum; Simian B disease; Site; Vaccines; Vietnam; Virulence; Virus; Week; aged; aquatic bird; attenuation; base; day; immunogenicity; influenza virus vaccine; influenzavirus; pandemic disease; pandemic influenza; pre-clinical; preclinical study; programs; wild bird

We have generated candidate vaccines against H9N2, H5N1 and H7N3 influenza viruses. Based on promising preclinical data in mice and ferrets, clinical lots of these vaccines were generated for Phase I clinical trials of the safety and immunogenicity of the vaccines for healthy adults under an IND. H9N2 cold-adapted (ca) vaccine: A Phase I study was initiated in 50 healthy adults who were admitted to an in-patient unit. The vaccine was safe and well tolerated but the level of replication was low. Despite this, the H9N2 ca vaccine induced serum antibody in over 90% of seronegative subjects who received two doses of vaccine. H5N1 cold-adapted (ca) vaccines: Three candidate vaccines were developed based on H5N1 viruses isolated in 1997, 2003 and 2004. In each virus, the HA and NA genes were derived from wild-type H5N1 viruses. The HA in each case was modified to remove the multibasic amino acid cleavage site that is a virulence motif. A Phase I trial for safety, infectivity, and immunogenicity of the 2004 H5N1 Vaccine based on the A/VietNam/1203/2004 (H5N1) virus, was undertaken at a dose of 106.7 TCID50 per dose in 20 healthy adults, aged 18-49 years. The clinical trial was conducted in an isolation unit. Subjects received two doses of vaccine, administered 28 to 62 days apart, and were sequestered in an isolation unit 3 weeks following both doses. The level of replication, infectivity, and immunogenicity of the vaccine virus at this dose were low. Therefore, a study was undertaken to evaluate the safety, infectivity and immunogenicity of a moderately higher dose (107.5 TCID50) of the same vaccine. Nineteen subjects received two doses of this dose. The vaccine was safe & well tolerated. Analysis of data from this study is in progress. In order to determine whether the finding of low infectivity and low immunogenicity observed with the 2004 H5N1 ca virus was unique to this strain, a Phase I study was undertaken with the 2003 H5N1 ca vaccine. Sixteen subjects received 2 doses of the 2003 H5N1 ca vaccine. The study is in progress. H7N3 cold-adapted (ca) vaccine: Based on promising preclinical data in mice and ferrets, an IND was submitted for a Phase I study to evaluate safety, level of replication, infectivity and immunogenicity of an H7N3 ca vaccine based on A/chicken/British Columbia/CN-6/2004 (H7N3). The study will be initiated in September 2007.

我们已经研制出针对H9N2、H5N1和H7N3流感病毒的候选疫苗。基于在小鼠和雪貂身上有希望的临床前数据，在IND下，为健康成年人疫苗的安全性和免疫原性的第一阶段临床试验产生了大量的临床疫苗。 H9n2冷适应(Ca)疫苗：一项第一阶段研究在50名住进病房的健康成年人中启动。该疫苗是安全的，耐受性良好，但复制水平很低。尽管如此，在接种了两剂疫苗的血清阴性受试者中，h9n2ca疫苗诱导了90%以上的血清抗体。 H5N1冷适应(Ca)疫苗：根据1997年、2003年和2004年分离的H5N1病毒开发了三种候选疫苗。在每种病毒中，HA和NA基因都来自野生型H5N1病毒。每种情况下的HA都被修饰，以去除作为毒力基序的多碱性氨基酸裂解位点。以A/越南/1203/2004(H5N1)病毒为基础的2004年H5N1疫苗的安全性、传染性和免疫原性的I阶段试验在20名18-49岁的健康成年人中进行，每剂106.7 TCID50。临床试验是在隔离病房进行的。受试者接种两剂疫苗，间隔28至62天，并在两剂疫苗接种后3周被隔离在隔离单元中。在这个剂量下，疫苗病毒的复制水平、传染性和免疫原性都很低。因此，开展了一项研究，以评估中等较高剂量(107.5 TCID50)同一疫苗的安全性、传染性和免疫原性。19名受试者接受了两次这种剂量的治疗。疫苗是安全的，耐受性良好。这项研究的数据分析正在进行中。 为了确定2004年H5N1 CA病毒的低传染性和低免疫原性是否是该毒株所特有的，对2003年H5N1 CA疫苗进行了I期研究。16名受试者接种了2剂2003年H5N1 CA疫苗。研究正在进行中。 H7N3冷适应(Ca)疫苗：基于在小鼠和雪貂身上有希望的临床前数据，IND被提交进行第一阶段研究，以评估基于A/FICE/British Columbia/CN-6/2004(H7N3)的H7N3ca疫苗的安全性、复制水平、传染性和免疫原性。这项研究将于2007年9月启动。