PDF(Pubmed)
Abstract：
UNASSIGNED: Falciparum malaria remains a global health problem. Two vaccines, based on the circumsporozoite antigen, are available. RTS, S/AS01 was recommended for use in 2021 following the advice of the World Health Organisation (WHO) Strategic Advisory Group of Experts (SAGE) on Immunization and WHO Malaria Policy Advisory Group (MPAG). It has since been pre-qualified in 2022 by the WHO. R21 is similar to RTS, S/AS01, and recently licensed in Nigeria, Ghana and Burkina Faso following Phase 3 trial results.
UNASSIGNED: We conducted a Phase 1b age de-escalation, dose escalation bridging study after a change in the manufacturing process for R21. We recruited healthy adults and children and used a three dose primary vaccination series with a booster dose at 1-2 years. Variable doses of R21 and adjuvant (Matrix-M ™) were administered at 10µgR21/50 µg Matrix-M™, 5µgR21/25µg Matrix-M™ and 5µgR21/50µg Matrix-M™ to 20 adults, 20 children, and 51 infants.
UNASSIGNED: Self-limiting adverse events were reported relating to the injection site and mild systemic symptoms. Two serious adverse events were reported, neither linked to vaccination. High levels of IgG antibodies to the circumsporozoite antigen were induced, and geometric mean titres in infants, the target group, were 1.1 (0.9 to 1.3) EU/mL at day 0, 10175 (7724 to 13404) EU/mL at day 84 and (following a booster dose at day 421) 6792 (5310 to 8687) EU/mL at day 456.
UNASSIGNED: R21/Matrix-M™ is safe, and immunogenic when given at varied doses with the peak immune response seen in infants 28 days after a three dose primary vaccination series given four weeks apart. Antibody responses were restored 28 days after a 4 th dose given one year post a three dose primary series in the young children and infants.
UNASSIGNED: Clinicaltrials.gov (NCT03580824; 9 th of July 2018; Pan African Clinical Trials Registry (PACTR202105682956280; 17 th May 2021).
UNASSIGNED: We conducted a Phase 1b age de-escalation, dose escalation bridging study after a change in the manufacturing process for R21. We recruited healthy adults and children and used a three dose primary vaccination series with a booster dose at 1-2 years. Variable doses of R21 and adjuvant (Matrix-M ™) were administered at 10µgR21/50 µg Matrix-M™, 5µgR21/25µg Matrix-M™ and 5µgR21/50µg Matrix-M™ to 20 adults, 20 children, and 51 infants.
UNASSIGNED: Self-limiting adverse events were reported relating to the injection site and mild systemic symptoms. Two serious adverse events were reported, neither linked to vaccination. High levels of IgG antibodies to the circumsporozoite antigen were induced, and geometric mean titres in infants, the target group, were 1.1 (0.9 to 1.3) EU/mL at day 0, 10175 (7724 to 13404) EU/mL at day 84 and (following a booster dose at day 421) 6792 (5310 to 8687) EU/mL at day 456.
UNASSIGNED: R21/Matrix-M™ is safe, and immunogenic when given at varied doses with the peak immune response seen in infants 28 days after a three dose primary vaccination series given four weeks apart. Antibody responses were restored 28 days after a 4 th dose given one year post a three dose primary series in the young children and infants.
UNASSIGNED: Clinicaltrials.gov (NCT03580824; 9 th of July 2018; Pan African Clinical Trials Registry (PACTR202105682956280; 17 th May 2021).
摘要：
恶性疟疾仍然是一个全球性的健康问题。两种疫苗,基于环子孢子抗原，是可用的。RTS,根据世界卫生组织（世卫组织）免疫战略咨询专家组（SAGE）和世卫组织疟疾政策咨询小组（MPAG）的建议，建议在2021年使用S/AS01。此后，它已在2022年获得世界卫生组织的资格预审。R21类似于RTS，S/AS01，最近在尼日利亚获得许可，加纳和布基纳法索遵循3期试验结果。
■我们进行了1b阶段的年龄降级，R21制造工艺改变后的剂量递增桥接研究。我们招募了健康的成人和儿童，并在1-2年时使用了三剂初级疫苗系列，并加强了剂量。可变剂量的R21和佐剂（Matrix-M™）以10µgR21/50µgMatrix-M™施用，5µgR21/25µgMatrix-M™和5µgR21/50µgMatrix-M™适用于20名成人，20个孩子,51个婴儿
■报告了与注射部位和轻度全身症状有关的自限性不良事件。报告了两个严重不良事件，与疫苗接种无关。诱导了高水平的环子孢子抗原IgG抗体，和婴儿的几何平均滴度，目标群体,在第0天为1.1（0.9至1.3）EU/mL，在第84天为10175（7724至13404）EU/mL，在第456天为6792（5310至8687）EU/mL。
■R21/Matrix-M™是安全的，以不同剂量给予时具有免疫原性，在间隔四周的三剂量初次疫苗系列接种后28天，婴儿的免疫反应达到峰值。在幼儿和婴儿中,在三次剂量初始系列后1年给予第4次剂量后28天,抗体应答恢复。
■Clinicaltrials.gov（NCT03580824；2018年7月9日；泛非临床试验注册（PACTR202105682956280；2021年5月17日）。
■我们进行了1b阶段的年龄降级，R21制造工艺改变后的剂量递增桥接研究。我们招募了健康的成人和儿童，并在1-2年时使用了三剂初级疫苗系列，并加强了剂量。可变剂量的R21和佐剂（Matrix-M™）以10µgR21/50µgMatrix-M™施用，5µgR21/25µgMatrix-M™和5µgR21/50µgMatrix-M™适用于20名成人，20个孩子,51个婴儿
■报告了与注射部位和轻度全身症状有关的自限性不良事件。报告了两个严重不良事件，与疫苗接种无关。诱导了高水平的环子孢子抗原IgG抗体，和婴儿的几何平均滴度，目标群体,在第0天为1.1（0.9至1.3）EU/mL，在第84天为10175（7724至13404）EU/mL，在第456天为6792（5310至8687）EU/mL。
■R21/Matrix-M™是安全的，以不同剂量给予时具有免疫原性，在间隔四周的三剂量初次疫苗系列接种后28天，婴儿的免疫反应达到峰值。在幼儿和婴儿中,在三次剂量初始系列后1年给予第4次剂量后28天,抗体应答恢复。
■Clinicaltrials.gov（NCT03580824；2018年7月9日；泛非临床试验注册（PACTR202105682956280；2021年5月17日）。
