A randomized Phase I/II study to evaluate safety and reactogenicity of a heat-stable rotavirus vaccine in healthy adults followed by evaluation of the safety, reactogenicity, and immunogenicity in infants
A randomized Phase I/II study to evaluate safety and reactogenicity of a heat-stable rotavirus vaccine in healthy adults followed by evaluation of the safety, reactogenicity, and immunogenicity in infants
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DOI：
10.1080/21645515.2019.1664239
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发表时间：
2019-10-28
影响因子：
4.8
通讯作者：
Clemens, John D.
中科院分区：
文献类型：
--
作者：
Kanchan, Vibhu;Zaman, Khalequ;Clemens, John D.
目的：评估18-45岁健康成人单次口服热稳定轮状病毒疫苗（HSRV）的安全性和反应原性，随后评估6-8周龄健康婴儿三剂HSRV的安全性、反应原性和免疫原性。试验设计：单中心随机对照，顺序，盲法（成人）和开放标签（婴儿）。环境：孟加拉国国际腹泻病研究中心的单一站点（icddr,b）。参与者：50名符合条件的成年人按1:1比例随机分配（HSRV：安慰剂），随后50名符合条件的婴儿按1:1比例随机分配(HSRV：比较剂（RotaTeq （R)，五价人牛（WC3）重组轮状病毒减毒活疫苗））。干预：成年人接受单剂量HSRV或安慰剂，随访14天。婴儿接受三剂HSRV或比较剂，每次剂量后随访28天。主要结局指标：主动和非主动不良事件（ae）以及任何严重不良事件（sae）是成人和婴儿安全性和反应原性评估的一部分，而血清抗轮状病毒IgA应答率仅是婴儿免疫原性评估的一部分。疫苗接种后，成人和婴儿中轮状病毒株的粪便脱落也被确定。结果：在这项研究中，与安慰剂相比，HSRV没有导致成人不良事件（ae）的增加。在婴儿中，HSRV的安全性与比较物相对于征求的ae相似。在婴儿中，在HSRV受者中未检测到疫苗病毒株的粪便脱落，但在两个比较受者中观察到。HSRV组婴儿血清抗轮状病毒IgA滴度从基线到剂量3后1个月上升3倍的百分比为88%(22/25)，比较组为84%（21/25）。结论：HSRV在成人和婴儿中普遍耐受良好，在婴儿中具有免疫原性。
Objectives: To assess the safety and reactogenicity of single oral dose of heat-stable rotavirus vaccine (HSRV) in healthy adults aged 18-45 years followed by assessment of safety, reactogenicity, and immunogenicity of three doses of HSRV in healthy infants aged 6-8 weeks at enrollment. Trial Design: Single-center randomized controlled, sequential, blinded (adults) and open-label (infants). Setting: Single site at International Center for Diarrheal Disease Research, Bangladesh (icddr,b). Participants: Fifty eligible adults randomized in 1:1 ratio (HSRV: Placebo) followed by 50 eligible infants randomized in 1:1 ratio (HSRV: Comparator (RotaTeq (R), pentavalent human-bovine (WC3) reassortant live-attenuated, rotavirus vaccine)). Intervention: Adults received either a single dose of HSRV or placebo and followed for 14 days. Infants received three doses of either HSRV or comparator with a follow-up for 28 days after each dose. Main Outcome Measures: Solicited and unsolicited adverse events (AEs) along with any serious adverse events (SAEs) were part of the safety and reactogenicity assessment in adults and infants whereas serum anti-rotavirus IgA response rates were part of immunogenicity assessment in infants only. Post-vaccination fecal shedding of vaccine-virus rotavirus strains was also determined in adults and infants. Results: In this study, HSRV, when compared with placebo, did not result in increase in solicited adverse events (solicited AEs) in adults. In infants, HSRV had a safety profile similar to comparator vis-a-vis solicited AEs. In infants, fecal shedding of vaccine-virus strains was not detected in HSRV recipients but was observed in two comparator recipients. Percentage of infants exhibiting threefold rise in serum anti-rotavirus IgA titers from baseline to 1-month post-dose 3 in HSRV group was 88% (22/25) and 84% (21/25) in comparator group. Conclusion: HSRV was found to be generally well-tolerated in both adults and infants and immunogenic in infants.