INFLUENZA CVD 9000

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。项目概述（摘要）：流感是一种常见的呼吸道传染病，由几种相关病毒引起。流感每年冬天都会流行，美国每年平均造成约36，000人死亡。这些死亡大多发生在老年人和患有慢性病，特别是肺和心脏病的所有年龄的人中。目前的流感病毒疫苗保护老年人免受流感，但没有达到预期效果。试图增加保护的一个考虑因素是增加疫苗剂量，但有人担心增加剂量可能会增加对疫苗的反应（如手臂疼痛，疼痛或发烧）。一家获得许可的美国流感疫苗制造商（Aventis Pasteur）已经制备了一种实验性流感病毒疫苗，其剂量比目前使用的剂量高出约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，与普通疫苗相比，高剂量疫苗耐受性良好，仅注射部位反应增加。自2002年的研究以来，高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反应很小，但这需要确定。还需要证明这种疫苗是否比标准剂量的流感疫苗刺激血液中更高水平的抗感染蛋白（或抗体）。美国国立卫生研究院（NIAID/NIH）下属的国家过敏和传染病研究所正在赞助这项研究。本研究的目的是比较接种单剂量标准流感疫苗或实验性高剂量疫苗的受试者的反应和抗体应答。实验性疫苗包含的三种流感病毒蛋白中每一种的量大约是标准疫苗中的四倍。标准疫苗和高剂量疫苗都含有美国FDA推荐用于2004-2005流感季节的三种流感病毒蛋白。本研究将在全国范围内招募约400例受试者。本研究在以下4个地点进行：马里兰州大学贝勒医学院辛辛那提医院医疗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、活性对照试验进行。年龄≥ 65岁、符合本研究入选标准的非卧床志愿者将随机（1：1）接受高剂量（60 mcg/病毒株）或标准剂量（15 mcg/病毒株）Aventis Pastuer 2004-2005三价灭活流感疫苗单次IM注射。受试者将在免疫接种后在诊所观察至少20分钟，并将在免疫接种后7天内保持记忆辅助，以记录每日口腔温度和任何全身和局部反应。将在免疫后8至12天通过电话联系志愿者，以审查其7天记忆辅助，包括评估其每日口腔温度、任何局部或全身反应以及任何其他AE的发生。志愿者将在第28天返回进行采血，以进行免疫原性评价。在约6个月时，志愿者将返回研究中心或通过电话联系以评估SAE的发生。研究完成后，将免费为前受试者提供一剂2005-2006年流感疫苗。

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.