印度婴幼儿使用即用型牛-人重配五价轮状病毒疫苗（ROTASIIL-Liquid）的免疫原性和批间一致性。
Immunogenicity and lot-to-lot consistency of a ready to use liquid bovine-human reassortant pentavalent rotavirus vaccine (ROTASIIL - Liquid) in Indian infants.
机构信息
Vadu Rural Health Program, KEM Hospital Research Centre, Vadu, Pune, India.
The Wellcome Trust Research Laboratory, Christian Medical College Vellore, India.
出版信息
Vaccine. 2019 May 1;37(19):2554-2560. doi: 10.1016/j.vaccine.2019.03.067. Epub 2019 Apr 4.
BACKGROUND
A lyophilized bovine-human rotavirus reassortant pentavalent vaccine (BRV-PV, Rotasiil®) was licensed in 2016. A liquid formulation of this vaccine (LBRV-PV, Rotasiil - Liquid) was subsequently developed and was tested for non-inferiority to Rotasiil® and for lot-to-lot consistency.
METHODS
This Phase II/III, open label, randomized study was conducted at seven sites across India from November 2017 to June 2018. Participants were randomized into four arms; Lots A, B, and C of LBRV-PV and Rotasiil® in 1:1:1:1 ratio. Three doses of study vaccines were given at 6, 10, and 14 weeks of age. Blood samples were collected four weeks after the third dose to assess rotavirus IgA antibody levels. Non-inferiority of LBRV-PV to Rotasiil was proven if the lower limit two-sided 95% confidence interval (CI) of geometric mean concentration (GMC) ratio was at least 0.5. Lot-to-lot consistency was proven if 95% CI of the GMC ratios of three lots were between 0.5 and 2. Solicited reactions were collected by using diary cards.
RESULTS
Of the 1500 randomized infants, 1436 infants completed the study. The IgA GMC ratio of LBRV-PV to Rotasiil® was 1.19 (95% CI 0.96, 1.48). The corresponding IgA seropositivity rates were 60.41% (57.41, 63.35) and 52.75% (47.48, 57.97). The IgA GMC ratios among the three LBRV-PV lots were: Lot A versus Lot B: 1.34 (1.03, 1.75); Lot A versus Lot C: 1.22 (0.93, 1.60); and Lot B versus Lot C: 0.91 (0.69, 1.19). The 95% CIs for the GMC ratios were between 0.69 and 1.75. The incidence of solicited reactions was comparable across the four arms. Only one serious adverse event of gastroenteritis event in the Rotasiil® group was causally related.
CONCLUSION
The immunological non-inferiority of LBRV-PV against Rotasiil® as well as lot-to-lot consistency of LBRV-PV was demonstrated. LBRV-PV had safety profile similar to Rotasiil®.
TRIAL REGISTRATION NUMBER
Clinical Trials.Gov [NCT03474055] and Clinical Trial Registry of India [CTRI/2017/10/010104].
背景
一种冻干的牛-人轮状病毒重组五价疫苗（BRV-PV，Rotasiil®）于 2016 年获得许可。随后开发了这种疫苗的液体配方（LBRV-PV，Rotasiil-Liquid），并对其进行了非劣效性测试，以证明其与 Rotasiil®和批间一致性。
方法
这项 II/III 期、开放标签、随机研究于 2017 年 11 月至 2018 年 6 月在印度的七个地点进行。参与者被随机分为四组；LBRV-PV 的 A、B 和 C 批和 Rotasiil®以 1:1:1:1 的比例分配。在 6、10 和 14 周龄时给予三种研究疫苗。在第三次剂量后四周收集血液样本，以评估轮状病毒 IgA 抗体水平。如果 LBRV-PV 与 Rotasiil 的几何平均浓度（GMC）比值的下限双侧 95%置信区间（CI）至少为 0.5，则证明 LBRV-PV 非劣效于 Rotasiil。如果三个批次的 GMC 比值的 95%CI 在 0.5 到 2 之间，则证明了批间一致性。通过使用日记卡收集应征反应。
结果
在 1500 名随机婴儿中，有 1436 名婴儿完成了研究。LBRV-PV 与 Rotasiil®的 IgA GMC 比值为 1.19（95%CI 0.96，1.48）。相应的 IgA 血清阳性率为 60.41%（57.41，63.35）和 52.75%（47.48，57.97）。三个 LBRV-PV 批次之间的 IgA GMC 比值分别为：Lot A 与 Lot B：1.34（1.03，1.75）；Lot A 与 Lot C：1.22（0.93，1.60）；Lot B 与 Lot C：0.91（0.69，1.19）。GMC 比值的 95%CI 在 0.69 到 1.75 之间。四个组之间应征反应的发生率相当。仅 Rotasiil®组有 1 例与胃肠炎事件相关的严重不良事件。
结论
证明了 LBRV-PV 对 Rotasiil®的免疫非劣效性以及 LBRV-PV 的批间一致性。LBRV-PV 具有与 Rotasiil®相似的安全性。
试验注册号
ClinicalTrials.gov [NCT03474055]和印度临床试验注册中心[CTRI/2017/10/010104]。
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