The effects of polyparasitism on vaccine response

说明(由申请人提供)：正在投入大量资源，以提高全球儿童疫苗接种覆盖率，但发展中国家儿童对标准疫苗接种的反应往往较弱。发展中社区的疫苗接种计划效率低下被归咎于冷链失误和缺乏可支持的基础设施，但慢性感染也起到了重要作用。多种母体寄生虫感染会影响未出生的婴儿，是潜在的重要疫苗反应调节剂，但尚未得到很好的研究。越来越多的证据表明，孕妇的慢性寄生虫感染，如血吸虫病、丝虫病、肠道蠕虫和疟疾，可以抑制胎儿和婴儿对后续感染和疫苗接种的免疫反应。寄生虫对免疫反应的影响机制尚不清楚，尽管寄生虫感染母亲的婴儿缺乏适当的疫苗反应似乎是由于母体免疫调节失调，从而导致胎儿免疫受损。有待检验的中心假设是，孕产妇和婴儿寄生虫感染的治疗将增强婴儿对疫苗接种的反应。我们建议对怀孕的肯尼亚妇女及其后代进行前瞻性研究，以评估寄生虫感染和及时抗寄生虫治疗对婴儿疫苗对脊髓灰质炎、流感嗜血杆菌和白喉的反应的影响。我们提出了以下具体目标：1)确定母体寄生虫感染对婴儿疫苗应答的单独和联合影响，以及2)测量母婴抗寄生虫治疗对婴儿疫苗应答的影响。该项目的长期目标是确定特定的产前和产后寄生虫治疗的价值，并开发新的方法来优化疫苗计划的有效性。

DESCRIPTION (provided by applicant): Extensive resources are being committed to improve global childhood vaccination coverage, but the response to standard vaccination is often diminished in children from developing nations. The ineffectiveness of vaccination programs in developing communities has been blamed on cold chain lapses and lack of supportable infrastructure, but chronic infections also play a significant role. Multiple maternal parasitic infections affect the unborn infant and are potentially important vaccine response modifiers, but have not been well studied. Increasing evidence suggests that chronic parasitic infections in pregnant women, such as schistosomiasis, filariasis, intestinal helminths, and malaria, can suppress fetal and infant immune responses to subsequent infections and vaccinations. The mechanisms of parasite effects on immune responses are not well understood, although the lack of appropriate vaccine response in infants of parasite-infected mothers appears to be due to dysregulation of maternal immunity, with resultant impaired fetal immunity. The central hypothesis to be tested is that treatment of maternal and infant parasitic infections will enhance infant responses to vaccination. We propose a prospective study of pregnant Kenyan woman and their offspring to evaluate the effects of parasitic infections and prompt anti-parasitic treatment on infant vaccine responses to polio, Haemophilus influenzae, and diphtheria. We propose the following specific aims: 1) to determine the individual and combined influence of maternal parasitic infections on infant vaccine responses, and 2) to measure the impact of maternal and infant anti-parasitic treatment on infant vaccine responses. The long term goals of this project are to determine the value of specific antenatal and postnatal parasitic treatments and to develop novel approaches to optimizing vaccine program effectiveness.