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):e040427. doi: 10.1136/bmjopen-2020-040427.
Drivers of lower vaccine efficacy and impaired vaccine-specific immune responses in low-income versus high-income countries, and in rural compared with urban settings, are not fully elucidated. Repeated exposure to and immunomodulation by parasite infections may be important. We focus on malaria, aiming to determine whether there are reversible effects of malaria infection on vaccine responses.
We have designed a randomised, double-blind, placebo-controlled, parallel group trial of intermittent preventive malaria treatment versus placebo, to determine effects on vaccine response outcomes among school-going adolescents (9 to 17 years) from malaria-endemic rural areas of Jinja district (Uganda). Vaccines to be studied comprise BCG vaccine on day 'zero'; yellow fever, oral typhoid and human papilloma virus vaccines at week 4; and tetanus/diphtheria booster vaccine at week 28. Participants in the intermittent preventive malaria treatment arm will receive dihydroartemisinin/piperaquine (DP) dosed by weight, 1 month apart, prior to the first immunisation, followed by monthly treatment thereafter. We expect to enrol 640 adolescents. 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. In secondary analyses, we will determine effects of monthly DP treatment (versus placebo) on correlates of protective immunity, on vaccine response waning, on whether there are differential effects on priming versus boosting immunisations, and on malaria infection prevalence. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of the intervention on vaccine responses.
Ethics approval has been obtained from relevant Ugandan and UK ethics committees. 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.
Current Controlled Trials identifier: ISRCTN62041885.
在低收入国家和高收入国家之间，以及在农村地区与城市地区相比，疫苗效力降低和疫苗特异性免疫反应受损的驱动因素尚未完全阐明。寄生虫感染的反复暴露和免疫调节可能很重要。我们专注于疟疾，旨在确定疟疾感染对疫苗反应是否存在可逆影响。
我们设计了一项随机、双盲、安慰剂对照、平行组试验，比较间歇性预防疟疾治疗与安慰剂，以确定在来自金贾区（乌干达）疟疾流行农村地区的上学青少年（9 至 17 岁）中，疟疾感染对疫苗反应结果的影响。将研究的疫苗包括零天接种卡介苗；第 4 周接种黄热病、口服伤寒和人乳头瘤病毒疫苗；第 28 周接种破伤风/白喉加强疫苗。间歇性预防疟疾治疗组的参与者将根据体重接受二氢青蒿素/哌喹（DP）给药，在第一次免疫接种前 1 个月给药，随后每月治疗一次。我们预计将招募 640 名青少年。主要结局是卡介苗接种后 8 周时 BCG 特异性干扰素-γ ELISpot 反应，以及其他疫苗接种后 4 周时关键疫苗抗原的抗体反应。在次要分析中，我们将确定每月 DP 治疗（与安慰剂相比）对保护性免疫的相关性、对疫苗反应衰减的影响、对初级免疫和加强免疫是否有不同影响，以及对疟疾感染流行率的影响。我们还将在参与者的亚组中进行探索性免疫学检测，以进一步描述干预措施对疫苗反应的影响。
已获得乌干达和英国相关伦理委员会的批准。结果将与乌干达卫生部、相关地区委员会、社区领导和研究参与者共享。进一步的传播将通过会议记录和出版物进行。
当前对照试验标识符：ISRCTN62041885。
