不含人血白蛋白（HSA）的水痘疫苗与含 HSA 制剂在生命第二年进行接种的安全性和免疫原性：一项 III 期、双盲、随机研究。

Safety and immunogenicity of a varicella vaccine without human serum albumin (HSA) versus a HSA-containing formulation administered in the second year of life: a phase III, double-blind, randomized study.

机构信息

NIHR Southampton Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK.

GSK, Avenue Fleming 20, B-1300, Wavre, Belgium.

出版信息

BMC Pediatr. 2019 Feb 7;19(1):50. doi: 10.1186/s12887-019-1425-7.

DOI:10.1186/s12887-019-1425-7

PMID:30732648

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6366055/

Abstract

BACKGROUND

A new formulation of the live-attenuated varicella vaccine Varilrix (GSK) produced without human serum albumin (HSA) was developed to minimize a theoretical risk of transmission of infectious diseases. A previous study showed that the vaccine was immunologically non-inferior to the HSA-containing vaccine and well-tolerated in toddlers; low-grade fever was numerically higher in children receiving the vaccine without HSA, but the study lacked power to conclude on this difference.

METHODS

In this phase III, double-blind, multi-center study, healthy 12-23-month-olds were randomized (1:1) to receive two doses of the varicella vaccine without (Var-HSA group) or with HSA (Var + HSA group) at days 0 and 42. The primary objective compared safety of the vaccines in terms of incidence of fever > 39.0 °C in the 15-day period post-first vaccination. The objective was considered met if the upper limit of the 95% confidence interval for the between-group difference in the incidence of fever > 39.0 °C was ≤5% (Var-HSA group minus Var + HSA group). Safety, reactogenicity and immune responses were evaluated.

RESULTS

Six hundred fifteen children in the Var-HSA group and 616 in the Var + HSA group received ≥1 vaccination. Fever > 39.0 °C was reported in 3.9 and 5.2% of participants in the Var-HSA and Var + HSA groups, with a between-group difference of - 1.29 (95% confidence interval: - 3.72-1.08); therefore, the primary objective was achieved. Fever rates post-each dose and the incidence of solicited local and general adverse events (AEs) were comparable between groups. Unsolicited AEs were reported for 43.9 and 36.5% of children in the Var-HSA group and 45.8 and 36.0% of children in the Var + HSA group, during 43 days post-dose 1 and 2, respectively. Serious AEs occurred in 2.1% (group Var-HSA) and 2.4% (group Var + HSA) of children, throughout the study. In a sub-cohort of 364 children, all had anti-varicella-zoster virus antibody concentrations ≥50 mIU/mL post-dose 2; comparable geometric mean concentrations were observed between the groups.

CONCLUSIONS

The varicella vaccine formulated without HSA did not induce higher rates of fever during the 15 day-post-vaccination period, as compared with the original HSA-containing vaccine. The two vaccines displayed similar safety and immunogenicity profiles in toddlers.

TRIAL REGISTRATION

NCT02570126 , registered on 5 October 2015 (www.clinicaltrials.gov).

摘要

背景

葛兰素史克公司（GSK）开发了一种不含人血清白蛋白（HSA）的新型减毒活水痘疫苗 Varilrix，旨在最大限度地降低传染病传播的理论风险。先前的研究表明，该疫苗在免疫原性上不劣于含 HSA 的疫苗，且在幼儿中耐受性良好；在接受无 HSA 的疫苗的儿童中，低等级发热的发生率较高，但该研究没有足够的效力来确定这种差异。

方法

在这项 III 期、双盲、多中心研究中，健康的 12-23 月龄婴儿以 1:1 的比例随机（分组）接受两次不含 HSA 的水痘疫苗（Var-HSA 组）或含 HSA 的疫苗（Var+ HSA 组），在第 0 天和第 42 天。主要终点是比较两种疫苗在第一次接种后 15 天内发热（体温>39.0°C）的安全性。如果发热（体温>39.0°C）发生率两组间差异的 95%置信区间上限（Var-HSA 组减去 Var+ HSA 组）≤5%，则认为主要终点达到。评估安全性、不良反应发生率和免疫反应。

结果

Var-HSA 组和 Var+ HSA 组各有 615 名和 616 名儿童接受了至少一次接种。Var-HSA 组和 Var+ HSA 组分别有 3.9%和 5.2%的参与者报告发热>39.0°C，组间差异为-1.29（95%置信区间：-3.72-1.08）；因此，主要终点达到。每组疫苗接种后的发热率和局部及全身不良事件（AE）的发生率在两组间相似。在第 1 次和第 2 次接种后 43 天，Var-HSA 组分别有 43.9%和 36.5%的儿童和 Var+ HSA 组分别有 45.8%和 36.0%的儿童报告了非预期 AE。在整个研究过程中，2.1%（Var-HSA 组）和 2.4%（Var+ HSA 组）的儿童发生了严重 AE。在 364 名儿童的亚组中，所有儿童在第 2 次接种后水痘-带状疱疹病毒抗体浓度均≥50 mIU/mL；两组间观察到的几何均数浓度相似。