Psychological Stress and Immune Response to Vaccination

描述（由申请人提供）：人们普遍认为，应激对免疫功能的影响是应激增加传染病易感性的主要生物学途径。然而，文献缺乏这一途径的经验证据，部分原因是未能关注与宿主耐药性发展相关的免疫措施。拟议研究的广泛目标是确定心理应激与体内免疫过程之间的联系途径，这些途径在临床上与对传染病的抵抗力的发展和维持有关。为此，采用乙型肝炎疫苗接种模型。该模型允许系统地探索将应激与暴露于新抗原后产生和维持一抗和二抗反应的能力联系起来的行为和生物学途径。它还允许探索个体差异对压力的生物反应程度在对压力-免疫关系的脆弱性中的作用。在这方面，已经证明个体在皮质醇的大小和对急性压力的免疫反应方面始终不同，可以想象，他们或多或少能够对疫苗接种产生抗体反应。128名年龄在40-60岁之间的健康男性和女性将被招募参加拟议的纵向研究，其中包括一个基于实验室的生理反应阶段，一个前瞻性监测阶段和一个随访期。在反应阶段，将测量参与者对急性实验室应激源的免疫和皮质醇反应，以确定对应激的免疫反应程度的个体差异。在这一阶段，参与者还将完成对近期生活压力和特质负面影响的自我报告。在监测阶段，参与者将按照标准方案接种三剂乙型肝炎疫苗。他们还将完成每次接种疫苗前后七天的每日压力日记，以评估急性压力水平。用于评估皮质醇水平的唾液样本将在每次接种疫苗时收集。将在第二次和第三次接种疫苗时以及在疫苗接种系列完成后6个月和12个月的随访期间测量抗体反应。

DESCRIPTION (provided by applicant): It is widely proposed that the influence of stress on immune function is the primary biological pathway linking stress to increased infectious disease susceptibility. However, the literature is missing empirical evidence for this pathway, in part because of a failure to focus on immune measures that are relevant for the development of host resistance. The broad objective of the proposed study is to identify pathways linking psychological stress to in vivo immune processes that are clinically relevant for the development and maintenance of resistance to infectious disease. For this purpose, a hepatitis B vaccination model is employed. This model permits the systematic exploration of behavioral and biological pathways linking stress to ability to mount and maintain primary and secondary antibody responses following exposure to a novel antigen. It also allows the exploration of the role that individual differences in the magnitude of biological responses to stress play in vulnerability to stress-immune relationship. In this regard, it has been demonstrated that individuals vary consistently in the magnitude of their cortisol and immune responses to acute stress, conceivably rending them more or less able to mount an antibody response to vaccination. One hundred and eight-two healthy males and females aged 40-60 years will be recruited to participate in the proposed longitudinal research, which includes a laboratory based physiological reactivity phase, a prospective surveillance phase and a follow-up period. In the reactivity phase, participant's immune and cortisol responses to an acute laboratory stressor will be measured to determine individual differences in the magnitude of immunologic reactivity to stress. During this phase, participants will also complete self-report measures of recent life stress and trait negative affect. In the surveillance phase, participants will be administered the three does of hepatitis B vaccine by standard protocol. They will also complete daily stress diaries for the seven days surrounding each dose of vaccine to assess levels of acute stress. Saliva samples for the assessment of cortisol levels will be collected at the time of each vaccination. Antibody responses will be measured at the time of the second and third does of vaccine and, during the follow-up period, 6 and 12 months following completion of the vaccination series.