Department of Biochemistry, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK; Centre for Clinical Vaccinology and Tropical Medicine, Jenner Institute, University of Oxford, Old Road Campus, Oxford OX3 7LE, UK; Kavli Institute for Nanoscience Discovery, University of Oxford, Dorothy Crowfoot Hodgkin Building, Oxford OX1 3QU, UK.
Interventions and Clinical Trials Department, Ifakara Health Institute, P.O. Box 74, Bagamoyo, Tanzania.
Med. 2023 Oct 13;4(10):668-686.e7. doi: 10.1016/j.medj.2023.07.003. Epub 2023 Aug 11.
RH5 is a leading blood-stage candidate antigen for a Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown.
A phase 1b, single-center, dose-escalation, age-de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania (NCT03435874). Between 12 April and 25 October 2018, 63 healthy adults (18-35 years), young children (1-6 years), and infants (6-11 months) received a priming dose of viral-vectored ChAd63 RH5 or rabies control vaccine. Sixty participants were boosted with modified vaccinia virus Ankara (MVA) RH5 or rabies control vaccine 8 weeks later and completed 6 months of follow-up post priming. Primary outcomes were the number of solicited and unsolicited adverse events post vaccination and the number of serious adverse events over the study period. Secondary outcomes included measures of the anti-RH5 immune response.
Vaccinations were well tolerated, with profiles comparable across groups. No serious adverse events were reported. Vaccination induced RH5-specific cellular and humoral responses. Higher anti-RH5 serum immunoglobulin G (IgG) responses were observed post boost in young children and infants compared to adults. Vaccine-induced antibodies showed growth inhibition activity (GIA) in vitro against P. falciparum blood-stage parasites; their highest levels were observed in infants.
The ChAd63-MVA RH5 vaccine shows acceptable safety and reactogenicity and encouraging immunogenicity in children and infants residing in a malaria-endemic area. The levels of functional GIA observed in RH5-vaccinated infants are the highest reported to date following human vaccination. These data support onward clinical development of RH5-based blood-stage vaccines to protect against clinical malaria in young African infants.
Medical Research Council, London, UK.
RH5 是恶性疟原虫疫苗的一个主要血期候选抗原；然而，其在疟疾流行地区的安全性和免疫原性尚不清楚。
在坦桑尼亚的巴加莫约进行了一项 1b 期、单中心、剂量递增、年龄递减、双盲、随机、对照试验（NCT03435874）。在 2018 年 4 月 12 日至 10 月 25 日期间，63 名健康成年人（18-35 岁）、幼儿（1-6 岁）和婴儿（6-11 个月）接受了病毒载体 ChAd63 RH5 或狂犬病对照疫苗的初免剂量。60 名参与者在 8 周后用改良痘苗病毒安卡拉（MVA）RH5 或狂犬病对照疫苗加强免疫，并在初免后完成 6 个月的随访。主要终点是接种后出现的有症状和无症状不良事件的数量以及研究期间出现的严重不良事件的数量。次要终点包括 RH5 免疫反应的衡量指标。
接种疫苗的耐受性良好，各组之间的情况相似。没有报告严重不良事件。接种疫苗可诱导 RH5 特异性细胞和体液免疫反应。与成年人相比，幼儿和婴儿在加强免疫后观察到更高的 RH5 血清免疫球蛋白 G（IgG）反应。疫苗诱导的抗体在体外对恶性疟原虫血期寄生虫具有生长抑制活性（GIA）；在婴儿中观察到的最高水平。
ChAd63-MVA RH5 疫苗在居住在疟疾流行地区的儿童和婴儿中表现出可接受的安全性和反应原性以及令人鼓舞的免疫原性。在 RH5 疫苗接种的婴儿中观察到的功能 GIA 水平是迄今为止人类接种疫苗后报告的最高水平。这些数据支持 RH5 为基础的血期疫苗的进一步临床开发，以保护非洲幼儿免受临床疟疾的侵害。
英国伦敦医学研究理事会。
