Nkurunungi Gyaviira, Zirimenya Ludoviko, Nassuuna Jacent, Natukunda Agnes, Kabuubi Prossy N, Niwagaba Emmanuel, Oduru Gloria, Kabami Grace, Amongin Rebecca, Mutebe Alex, Namutebi Milly, Zziwa Christopher, Amongi Susan, Ninsiima Caroline, Onen Caroline, Akello Florence, Sewankambo Moses, Kiwanuka Samuel, Kizindo Robert, Kaweesa James, Cose Stephen, Webb Emily, Elliott Alison M
Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda
Immunomodulation and Vaccines Programme, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.
BMJ Open. 2021 Feb 16;11(2):e040426. doi: 10.1136/bmjopen-2020-040426.
Several licensed and investigational vaccines have lower efficacy, and induce impaired immune responses, in low-income versus high-income countries and in rural, versus urban, settings. Understanding these population differences is essential to optimising vaccine effectiveness in the tropics. We suggest that repeated exposure to and immunomodulation by chronic helminth infections partly explains population differences in vaccine response.
We have designed an individually randomised, parallel group trial of intensive versus standard praziquantel (PZQ) intervention against schistosomiasis, to determine effects on vaccine response outcomes among school-going adolescents (9-17 years) from rural -endemic Ugandan islands. Vaccines to be studied comprise BCG on day 'zero'; yellow fever, oral typhoid and human papilloma virus (HPV) vaccines at week 4; and HPV and tetanus/diphtheria booster vaccine at week 28. The intensive arm will receive PZQ doses three times, each 2 weeks apart, before BCG immunisation, followed by a dose at week 8 and quarterly thereafter. The standard arm will receive PZQ at week 8 and 52. We expect to enrol 480 participants, with 80% infected with at the outset.Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. Secondary analyses will determine the effects of intensive anthelminthic treatment on correlates of protective immunity, on waning of vaccine response, on priming versus boosting immunisations and on infection status and intensity. Exploratory immunology assays using archived samples will enable assessment of mechanistic links between helminths and vaccine responses.
Ethics approval has been obtained from relevant ethics committes of Uganda and UK. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications.
ISRCTN60517191.
在低收入国家与高收入国家之间以及农村地区与城市地区，几种已获许可和正在研究的疫苗效力较低，且诱导的免疫反应受损。了解这些人群差异对于优化热带地区的疫苗效果至关重要。我们认为，长期接触慢性蠕虫感染并受到其免疫调节作用在一定程度上解释了疫苗反应的人群差异。
我们设计了一项针对血吸虫病的强化与标准吡喹酮（PZQ）干预的个体随机平行组试验，以确定对来自乌干达农村流行岛屿的在校青少年（9 - 17岁）疫苗反应结果的影响。待研究的疫苗包括在第“零”天接种卡介苗；在第4周接种黄热病、口服伤寒和人乳头瘤病毒（HPV）疫苗；在第28周接种HPV和破伤风/白喉加强疫苗。强化组将在卡介苗免疫前每隔2周接受3次PZQ剂量，随后在第8周再接受1次剂量，此后每季度接受1次剂量。标准组将在第8周和第52周接受PZQ。我们预计招募480名参与者，其中80%在开始时感染[具体寄生虫名称未给出]。主要结局是卡介苗免疫后8周的卡介苗特异性干扰素-γ酶联免疫斑点试验反应，以及其他疫苗免疫后4周对关键疫苗抗原的抗体反应。二次分析将确定强化驱虫治疗对保护性免疫相关因素、疫苗反应减弱、初次免疫与加强免疫以及[具体寄生虫名称未给出]感染状况和强度的影响。使用存档样本进行的探索性免疫学检测将能够评估蠕虫与疫苗反应之间的机制联系。
已获得乌干达和英国相关伦理委员会的伦理批准。结果将与乌干达卫生部、相关区议会、社区领袖和研究参与者分享。进一步传播将通过会议论文集和出版物进行。
ISRCTN60517191。
