IMMUNOGENICITY AND SAFETY OF A SPLIT, INACTIVATED, TRIVALENT INFLUENZA VACCINE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。背景：每年常规接种流感疫苗是一项长期建议，2004年，该建议扩展到6个月至2岁的儿童。任何希望减少感染流感风险的人也可接种疫苗。流感疫苗一经广泛使用，就一再被证明在降低流感相关发病率和死亡率方面非常有效。将流感疫苗建议的范围扩大到包括儿童，增加了生产所需的流感疫苗剂量。截至去年，美国只有两家获得FDA许可的流感疫苗制造商。2004年，由于其中一家制造商对疫苗生产的安全担忧，近50%的疫苗损失，疫苗供应严重受损。这些事件促使人们更加关注如何在美国增加流感疫苗的剂量。增加流感疫苗剂量的一种可能的方法是通过皮内注射（ID）而不是肌肉注射（IM）途径注射少量的流感疫苗。先前研究的数据表明，在健康成人中，只需3微克TIV（三价流感疫苗）给予ID，就能产生相当于标准剂量TIV（每15微克HA[血凝素]）给予IM的免疫反应。这项由美国国立卫生研究院赞助的研究的目的是，与通过肌肉注射流感疫苗的标准方法相比，通过皮内途径（就在皮肤下）注射较小剂量的流感疫苗是否会产生相当数量的抗流感抗体（细菌战士）。这项研究还将收集有关通过这些途径接种疫苗的相对安全性的信息。方法本研究将在18 ~ 64岁的健康成人中进行。每位受试者的参与将持续约21天。在获得知情同意后，参与者将被随机分配到4个疫苗组之一：1)使用Becton-Dickenson针和注射器皮下注射6 ug流感疫苗（BD ID系统），2)使用BD ID系统皮下注射9 ug流感疫苗，3)使用Mantoux技术注射3 ug流感疫苗，4)通过肌肉注射途径注射15 ug流感疫苗（对照组）。每位受试者将接种一剂流感疫苗。使用BD ID系统接受皮内注射疫苗的前两组将接受2004-2005年三价流感疫苗的试验性配方。另外两组将通过上述方法接种2004-2005年许可的三价流感疫苗Fluzone。流感疫苗由赛诺菲巴斯德公司提供。在接种流感疫苗前后约21天将采集血液样本。在获得第二次血液样本后，参与者将使用标准的肌肉注射途径获得2005-2006年流感疫苗（Fluzone；由赛诺菲巴斯德公司生产）的许可配方。

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. Background Routine yearly administration of flu vaccine is a long-standing recommendation and in 2004, the recommendation was extended to children 6 months to 2 years of ae. The vaccine may also be administered to anyone wishing to reduce the risk of contracting influenza. When widely used, influenza vaccines have repeatedly been shown to be highly effective at reducing influenza related morbidity and mortality. The extension of the influenza vaccine recommendation to include children has increased the number of influenza vaccine doses needed for production. As of last year, there were only 2 manufacturers of FDA licensed flu vaccine in the U.S. Vaccine supply was seriously compromised in 2004 when nearly 50% of the vaccine was lost due to safety concerns over vaccine production by 1 of the manufacturers. These events have led to a greater focus on finding ways to expand the number of available flu vaccine doses in the U.S. One possible way to increase the number of flu doses would be to administer smaller amounts of flu vaccine through the intradermal (ID) route (rather than the intramuscular [IM] route. Data from prior studies has shown that in healthy adults, as little as 3 ug of TIV (trivalent influenza vaccine) administered ID produced an immune response equivalent to a standard dose of TIV (15 ug per HA [hemaglutinin]) given IM. Purpose The purpose of this NIH-sponsored study is to find out if giving a smaller dose of flu vaccine through the intradermal route (just under the skin) will generate a comparable amount of antibodies (germ fighters) against flu as compared with the standard method of giving the flu vaccine through the intramuscular route. This study will also collect information about the relative safety of giving the vaccine through each of these routes. Methods The study will be conducted in healthy adults, 18 to 64 years of age. Each subject's participation will last approximately 21 days. After obtaining informed consent, participants will be randomized to one of 4 vaccine groups: 1) 6 ug of flu vaccine given intradermally with the Becton-Dickenson needle and syringe (BD ID system), 2) 9 ug of flu vaccine given intradermally with the BD ID System, 3) 3 ug of flu vaccine given ID using the Mantoux technique, and 4) 15 ug of flu vaccine given through the intramuscular route (control group). Each subject will receive a single dose of the flu vaccine. The first two groups who receive the vaccine intradermally using the BD ID system will receive an investigational formulation of the 2004-2005 trivalent flu vaccine. The second two groups will receive the licensed 2004-2005 trivalent flu vaccine, Fluzone, through the methods described above. The flu vaccines are provided by sanofi Pasteur. A blood sample will be obtained just prior to and approximately 21 days following administration of the flu vaccine. After the second blood sample is obtained, the participant will be offered the licensed formulation of the 2005-2006 flu vaccine (Fluzone; manufactured by sanofi Pasteur) using the standard intramuscular route.