INFLUENZA CVD 9000

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。项目简介(摘要)：流感是一种常见的呼吸道感染，由多种相关病毒引起。每年冬天都会发生流感疫情，美国每年平均约有3.6万人死于流感。这些死亡大多发生在老年人和患有慢性病的所有年龄段的人中，特别是肺病和心脏病。目前的流感病毒疫苗可以保护老年人免受流感侵袭，但效果并不理想。试图加强保护的一个考虑是增加疫苗剂量，但有人担心增加剂量可能会增加对疫苗的反应(如手臂酸痛、疼痛或发烧)。美国一家获得许可的流感疫苗制造商(安万特·巴斯德)已经准备好了一种实验性流感病毒疫苗，其剂量大约是目前使用剂量的4倍。2002年在老年受试者中进行的一项类似制备的高剂量疫苗的先前研究表明，与通常的疫苗相比，高剂量疫苗的耐受性良好，只是注射部位的反应增加。自2002年的研究以来，大剂量疫苗也不含标准疫苗中的防腐剂(硫柳汞)和明胶。预计这种疫苗接种后几乎没有反应，但这一点需要确定。还需要证明，这种疫苗是否能刺激血液中比标准剂量的流感疫苗更高水平的抗感染蛋白(或抗体)。国家卫生研究院(NIAID/NIH)下属的国家过敏和传染病研究所赞助了这项研究。这项研究的目的是比较接种单剂标准流感疫苗或实验性大剂量疫苗的受试者的反应和抗体反应。实验疫苗的含量大约是标准疫苗中三种流感病毒蛋白含量的四倍。标准疫苗和高剂量疫苗都含有美国FDA推荐的2004-2005年流感季节的三种流感病毒蛋白。约400名受试者将在全国范围内参加这项研究。本研究在以下4个地点进行(S)：马里兰大学贝勒医学院辛辛那提医院医学中心圣路易斯大学健康科学中心本临床试验将作为前瞻性、双盲、随机、积极对照试验进行。符合本研究入选标准的65岁及以上的流动志愿者将被随机(1：1)单次肌注高剂量(60mcg/病毒株)或标准剂量(15mcg/病毒株)的安万特Pastuer 2004-2005三价灭活流感疫苗。受试者将在免疫后在诊所观察至少20分钟，并将在接种当天后7天内保持记忆辅助设备，以记录每日口腔温度和任何全身和局部反应。志愿者将在接种疫苗后8至12天内通过电话联系他们，以回顾他们7天的记忆辅助工具，包括评估他们的日常口腔温度、任何局部或全身反应以及是否发生任何其他AEs。志愿者将在第28天回来抽血进行免疫原性评估。大约6个月后，志愿者将返回研究现场或通过电话联系，以评估SAE的发生情况。在研究完成后，以前的受试者将免费获得一剂2005-2006年的流行性感冒疫苗。

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. Description of Project (Abstract): Influenza is a common respiratory infection caused by several related viruses. Epidemics of influenza occur each winter and are responsible for an average of about 36,000 deaths each year in the United States. Most of these deaths occur among elderly persons and among people of all ages who suffer from chronic diseases, particularly of the lungs and the heart. Current influenza virus vaccines protect elderly persons against influenza, but not as well as desired. One consideration for trying to increase protection is to increase the vaccine dose, but there is some concern that increasing the dose may increase reactions to the vaccine (such as sore arm, aches, or fever). One of the licensed U.S. influenza vaccine manufacturers (Aventis Pasteur) has prepared an experimental influenza virus vaccine with a dose that is about 4 times higher than the currently used dose. A previous study with a similarly prepared high dose of the vaccine conducted in elderly subjects in 2002, showed that the high dose vaccine was well tolerated with only increased reactions at the injection site compared to the usual vaccine. Since the 2002 study, the high-dose vaccine has also been made without preservative (thimerosal) and gelatin, which are in the standard vaccine. It is expected that this vaccine can be given with little reaction, but this needs to be determined. It also needs to be shown whether such a vaccine stimulates higher levels of infection-fighting proteins (or antibodies) in the blood than standard doses of influenza vaccine. The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIAID/NIH) is sponsoring this research study. The purpose of this research study is to compare reactions and antibody responses in subjects who are vaccinated with either a single dose of a standard flu vaccine or the experimental high dose vaccine. The experimental vaccine includes approximately four times the amount of each of three influenza virus proteins that are in the standard vaccine. Both the standard vaccine and the high dose vaccine contain the three influenza virus proteins that were recommended by the U.S. FDA for the 2004-2005 influenza season. About 400 subjects will be enrolled in this study nationwide. This research study is being conducted at the following 4 places(s): ¿ The University of Maryland ¿ Baylor College of Medicine ¿ Cincinnati Hospital Medical Center ¿ St. Louis University Health Sciences Center This clinical trial will be conducted as a prospective, double-blind, randomized, active-controlled trial. Ambulatory volunteers, ages 65 years and older, who meet the entry criteria for this study, will be randomized (1:1) to receive a single IM injection of either the high-dose (60mcg/virus strain) or standard-dose (15mcg/virus strain) of Aventis Pastuer 2004-2005 trivalent inactivated influenza vaccine. Subjects will be observed in the clinic for at least 20 minutes after immunization and will maintain a memory aid to record daily oral temperature and any systemic and local reactions for 7 days after the day of immunization. Volunteers will be contacted by phone between 8 to 12 days after immunization to review their 7-day memory aid, including the assessment of their daily oral temperature, any local or systemic reactions and the occurrence of any other AEs. Volunteers will return at Day 28 for a blood draw for immunogenicity evaluations. At approximately 6 months, the volunteers will either return to the study site or be contacted by phone to assess the occurrence of SAEs. Following completion of the study, former subjects will be offered a dose of the 2005-2006 Fluzone vaccine at no charge.