INTRAMUSCULAR INACTIVATED INFLUENZA A/H5N1 VACCINE WITH DIFFERENT ADJUVANTS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这是一项随机、安慰剂对照、剂量范围的I/II期研究，对象为18岁至(含)的健康成年人。本研究旨在调查研究中的甲型H5N1流感灭活疫苗单独或与氢氧化铝或MF59佐剂联合使用时的安全性、反应性和剂量相关免疫原性。第二个目标是确定疫苗和佐剂的最佳剂量水平，以产生可接受的免疫原性反应，同时保持足够的安全性。在随后的研究中，这种剂量优化将同时适用于年轻和老年受试者群体。四个网站将在这项研究中招收受试者。 大约270名健康成年人将在2-4周内参加这项多中心、随机、安慰剂对照、剂量范围不等的临床试验。符合研究入选标准的受试者将被随机分成9组(见表)，分别接受60、30或15剂的生理盐水安慰剂或甲型H5N1流感疫苗；或15或7.5 g的甲型H5N1流感疫苗和MF59；或30、15或7.5 g氢氧化铝的甲型H5N1流感疫苗，按大致相等的比例肌注(N=30/疫苗剂量组总数270)。在第一次免疫接种之前，将采集实验室安全概况的血液。受试者将接受间隔约28天的两剂疫苗。疫苗管理将由一名非盲目的疫苗管理员执行，他不会参与后续评估。接种后将在诊所观察受试者至少15分钟，受试者将在每次接种后7天内保持记忆辅助器，以记录口腔温度和全身和局部AEs。受试者将在接种疫苗后1至3天(大约第2天)通过电话联系，以评估AEs的发生，他们将在第7天返回诊所进行AEs和伴随的药物评估、有针对性的体检(如果有指示)、安全实验室测试和记忆辅助检查。在每次接种疫苗后，将进行电话评估，以评估AEs。将在第一次免疫之前和之后约7天以及第二次免疫后7天获取用于安全实验室测试的血清。免疫原性评估的血清将在免疫前、第一次免疫后大约1个月、第二次免疫后大约1个月和6个月后获得。在开始接种第二剂疫苗之前，SMC将审查第一剂疫苗接种后7天内的所有可用安全性数据。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a randomized, placebo-controlled, dose-ranging, Phase I/II study in healthy adults, 18 to 64 years old, inclusive. This study is designed to investigate the safety, reactogenicity, and dose-related immunogenicity of an investigational inactivated influenza A/H5N1 virus vaccine when given alone or combined with the adjuvants aluminum hydroxide or MF59. A secondary goal is to identify an optimal dose level of the vaccine and the adjuvant that generates an acceptable immunogenic response while maintaining an adequate safety profile. This dose optimization will be applied to both younger and older subject populations in subsequent studies. Four sites will enroll subjects in this study. Approximately 270 healthy adults, will be enrolled over a 2-4 week period into this multicenter, randomized, placebo-controlled, dose-ranging clinical trial. Subjects who meet the entry criteria for the study will be randomized into 9 groups (see table) to receive two doses of saline placebo or influenza A/H5N1 vaccine at 60, 30, or 15 >g; or influenza A/H5N1 vaccine at 15 or 7.5 >g with MF59; or influenza A/H5N1 vaccine with aluminum hydroxide at 30, 15, or 7.5 >g by IM injection in an approximate equal ratio (N=30/vaccine dose group total 270). Blood for a laboratory safety profile will be drawn prior to the first immunization. Subjects will receive 2 doses separated by approximately 28 days. Vaccine administration will be performed by an unblinded vaccine administrator, who will not be involved in subsequent assessments. Subjects will be observed in the clinic for at least 15 minutes after inoculation, and subjects will maintain a memory aid to record oral temperature and systemic and local AEs for 7 days after each immunization. Subjects will be contacted by telephone 1 to 3 days after vaccination (approximately Day 2) to assess for the occurrence of AEs, and they will return to the clinic on Day 7 for AE and concomitant medication assessment, a targeted physical examination (if indicated), safety laboratory tests and a review of the memory aid. Telephone calls to assess AEs will be performed following each vaccination. Serum for safety laboratory tests will be obtained prior to and approximately 7 days following first immunization and 7 days following second immunization. Serum for Immunogenicity evaluations will be obtained prior to immunization, approximately 1 month after first immunization and approximately 1 month and 6 months after second immunization. All available 7 day safety data following the first dose of the vaccine will be reviewed by a SMC prior to initiation of administration of the second dose of vaccine.