Maternal Stress, Obesity, and Influenza Virus Vaccine Immunogenicity in Pregnancy

描述（由申请人提供）：建议所有孕妇接种季节性三价流感病毒疫苗（TIV），因为孕妇被认为存在流感并发症、住院和死亡的高风险。怀孕期间接种疫苗也可以为0-6个月的婴儿提供保护，这是一个未批准接种疫苗的高风险群体。然而，实际上没有关于足够的母体抗体反应或足够的抗体转移到新生儿的预测因素的数据。对未怀孕成人和动物的研究以及我们自己关于孕妇TIV后抗体反应的初步数据表明，心理社会压力和肥胖是值得关注的两个关键风险因素。 研究设计：我们将研究心理社会压力和肥胖对1）孕妇对TIV的抗体反应和2）抗体从母亲转移到新生儿的影响。本研究将纳入180名女性（90名肥胖，90名非肥胖），这些女性将在妊娠中期（妊娠13-28周）接种疫苗。将在接种前、接种后1个月和分娩时评估母体抗体水平。新生儿抗体水平将在分娩时通过脐带血测量。将在三个流感季节收集数据。在每个季节，将评估60名妇女; 30名肥胖和30名非肥胖妇女，她们在年龄、种族、产次和社会经济地位方面相似。每年针对A/H1N1、A/H3 N2和B毒株的抗流感抗体滴度将通过血凝抑制（HAI）试验测定。 假设1：在孕妇中，压力和肥胖都预示着TIV后一个月获得保护性抗体应答的可能性降低。肥胖的影响在高度紧张的女性中最为明显。假设二：更大的母亲压力和肥胖将预测新生儿脐带血中保护性抗体水平降低的可能性，在同时具有这两种风险因素的人群中影响最大。我们将研究可能导致新生儿效应的四种途径：1）母体抗体应答强度受损（假设1），2）从接种后1个月至分娩期间母体抗体水平维持较差，3）母胎传播效率较低（新生儿脐带血/母体抗体比率），以及4）早产率较高。 本研究测试了创新的假设，即心理社会压力和肥胖严重损害母体抗体反应和抗体水平的新生儿后，母亲在怀孕期间接种流感疫苗。如果我们的假设得到证实，我们将确定和量化新的风险因素对两个易患流感并发症的人群（孕妇和婴儿）免疫保护不良的影响。高剂量疫苗或两个剂量的时间表，现在可用于其他高风险群体谁显示对传统的TIV反应差，包括老年人，儿童和移植受体。这项研究将确定是否有理由重新评估针对具有特定风险因素的孕妇的流感疫苗建议。

DESCRIPTION (provided by applicant): Seasonal trivalent influenza virus vaccine (TIV) is recommended for all pregnant women because they are considered at high risk for complications, hospitalization, and death from influenza. Vaccination in pregnancy can also provide protection for infants from 0-6 months, a high risk group for whom vaccination is not approved. However, there are virtually no data on predictors of adequate maternal antibody response or sufficient antibody transfer to the newborn. Studies of nonpregnant adults and animals as well as our own preliminary data on antibody responses following TIV in pregnant women demonstrate that psychosocial stress and obesity are two key risk factors that warrant attention in this regard. Study Design: We will examine effects of psychosocial stress and obesity on 1) antibody responses to TIV in pregnant women and 2) antibody transfer from the mother to the newborn. This study will include 180 women (90 obese, 90 non-obese) who will be vaccinated during the 2nd trimester of pregnancy (13-28 weeks gestation). Maternal antibody levels will be assessed prior to vaccination, at one month post-vaccination and at the time of delivery. Newborn antibody levels will be measured via cord blood at the time of delivery. Data will be collected across three influenza seasons. In each season, 60 women will be assessed; 30 obese and 30 non-obese who will be similar in age, race, parity, and socioeconomic status. Anti-influenza antibody titers to A/H1N1, A/H3N2, and B strains in each year will be determined by the hemagglutination inhibition (HAI) test. Hypothesis 1: Among pregnant women, both stress and obesity will predict decreased likelihood of achieving a protective antibody response at one month after TIV. Effects of obesity will be the most pronounced among highly stressed women. Hypothesis 2: Greater maternal stress and obesity will predict decreased likelihood of protective antibody levels in newborn cord blood, with the most robust effects among those with both risk factors. We will examine four pathways which may contribute to effects in newborns: 1) impaired magnitude of maternal antibody response (Hypothesis 1), 2) poorer maintenance of maternal antibody levels from one month post-vaccination to delivery, 3) less efficient maternal-fetal transmission (newborn cord blood/maternal antibody ratio), and 4) higher rates of preterm birth. This study tests the innovative hypotheses that psychosocial stress and obesity substantially impair maternal antibody responses and antibody levels in newborns following maternal influenza vaccination in pregnancy. If our hypotheses are confirmed, we will identify and quantify the impact of novel risk factors for poor immune protection in two populations vulnerable to influenza complications, pregnant women and infants. High dose vaccine or two dose schedules are now available for other high risk groups who show poor responses to traditional TIV including older adults, children, and transplant recipients. This study will determine if it is justified to re-evaluate influenza vaccine recommendations for pregnant women with specific risk factors.