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.

我们已经研制出了针对H9 N2、H5 N1和H7 N3流感病毒的候选疫苗。基于小鼠和雪貂中有希望的临床前数据，生成了这些疫苗的临床批次，用于IND下健康成人疫苗安全性和免疫原性的I期临床试验。 H9 N2冷适应（ca）疫苗：在50名住院的健康成年人中启动了一项I期研究。 该疫苗安全且耐受性良好，但复制水平较低。 尽管如此，H9 N2 ca疫苗在接受两剂疫苗的血清阴性受试者中诱导了超过90%的血清抗体。 H5 N1冷适应（ca）疫苗：根据1997年、2003年和2004年分离的H5 N1病毒开发了三种候选疫苗。在每种病毒中，HA和NA基因均来源于野生型H5 N1病毒。在每种情况下，HA被修饰以去除作为毒力基序的多碱基氨基酸切割位点。在20名18-49岁的健康成人中进行了基于A/Vietnam/1203/2004（H5 N1）病毒的2004 H5 N1疫苗的安全性、感染性和免疫原性的I期试验，剂量为106.7 TCID 50/剂。临床试验在隔离病房进行。 受试者接受两剂疫苗，间隔28至62天接种，并在两剂疫苗接种后3周隔离在隔离单元中。在该剂量下，疫苗病毒的复制水平、感染性和免疫原性均较低。因此，进行了一项研究，以评价中等较高剂量（107.5 TCID 50）相同疫苗的安全性、感染性和免疫原性。19例受试者接受了两次该剂量。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。 为了确定在2004年H5 N1 ca病毒中观察到的低感染性和低免疫原性的发现是否是该毒株特有的，对2003年H5 N1 ca疫苗进行了I期研究。16名受试者接种了2剂2003年H5 N1 ca疫苗。这项研究正在进行中。 H7 N3冷适应（ca）疫苗：基于小鼠和雪貂中有希望的临床前数据，提交了一份IND进行I期研究，以评价基于A/鸡/不列颠哥伦比亚省/CN-6/2004（H7 N3）的H7 N3 ca疫苗的安全性、复制水平、感染性和免疫原性。这项研究将于2007年9月开始。