Probiotics to Enhance Influenza Vaccine Immunogenicity

描述（由申请人提供）：65岁及以上的老年人约占流感和肺炎相关死亡的90%。在过去的20年里，由于美国人口老龄化，流感导致的死亡人数大幅增加。流感疫苗是预防流感的第一道防线。建议所有65岁及以上的成年人使用胃肠外接种的灭活流感疫苗（IIV），但经粘膜接种的减毒活流感疫苗（LAIV）在预防50岁及以上人群中的流感方面并不有效。即使在老年人群中同时接种IIV和LAIV的研究中，对两种疫苗的免疫应答仍有改善的空间。体外研究和动物数据表明，益生菌，特别是乳杆菌GG（LGG）， 具有免疫调节特性。来自健康志愿者的几项研究的初步数据表明，LGG增强了对粘膜接种疫苗的免疫反应，如口服伤寒沙门氏菌，轮状病毒和脊髓灰质炎病毒。 我们建议在65岁及以上的成年人中进行一项双盲随机安慰剂对照I/II期临床试验，以评估口服LGG是否能有效地增强 IIV单独或IIV和LAIV的组合的免疫原性。本研究将招募104例受试者，26例将接受IIV+LAIV +口服LGG，26例将接受IIV+LAIV和口服安慰剂，26例将接受IIV +口服LGG，26例将接受IIV和口服安慰剂。后两组还将接受经鼻给药的安慰剂，以匹配LAIV给药。每周采集血液和鼻标本，持续4周，以评价对免疫接种的初始粘膜和全身免疫应答。在流感季节结束时将采集额外的血液和鼻标本。在整个流感季节，受试者将在免疫接种后每两周接受一次随访，以评估症状，并在出现流感样疾病时采集标本进行病毒培养。这项研究有可能提供一种新的替代方法来提高老年人流感疫苗的免疫应答。

DESCRIPTION (provided by applicant): Older adults aged 65 and over account for approximately 90% of deaths associated with influenza and pneumonia. Deaths due to influenza have increased substantially over the last 20 years due to the aging of the population in the United States. The influenza vaccine is the first line of defense against influenza. The parenterally administered inactivated influenza vaccine (IIV) is recommended for all adults aged 65 and over, but the mucosally administered live attenuated influenza vaccine (LAIV) has not been shown to be efficious in the prevention of influenza in individuals aged 50 and older. Even in studies where both IIV and LAIV have been co-administered to the elderly population, there is room for improvement in the immune response to both vaccines. In vitro studies and animal data show that probiotics, particularly Lactobacillus GG (LGG), have immunomodulatory properties. Preliminary data from several studies of healthy volunteers suggest that LGG boosts the immune response to mucosally administered vaccines such as oral Salmonella typhi, rotavirus and polio virus. We propose to conduct a double-blind randomized placebo controlled Phase l/ll clinical trial in adults aged 65 and older to evaluate whether orally administered LGG is effective in enhancing the immunogenicity of either IIV alone or the combination of IIV and LAIV. One hundred and four subjects will be recruited into the study, 26 will receive IIV+LAIV + oral LGG, 26 will receive IIV+LAIV and oral placebo, 26 will receive IIV + oral LGG and 26 will receive IIV and oral placebo. The latter two groups will also receive a nasally administered placebo to match LAIV administration. Blood and nasal specimens will be collected weekly for four weeks to evaluate the initial mucosal and systemic immune response to the immunization. Additional blood and nasal specimens will be collected at the end of the influenza season. Subjects will be followed every two weeks following immunization throughout the influenza season to assess symptoms and have specimens obtained for viral culture if they develop influenza like illnesses. This study has the potential to provide insight into a novel alternative approach to improve the immune response of the influenza vaccines in the elderly.