Background

We evaluated the safety and immunogenicity of liquid and lyophilized formulations of an investigational trivalent group B streptococcus (GBS) vaccine in non-pregnant women and assessed the formulations’ equivalence in terms of serotype-specific immune response.

Methods

This phase II, randomized, comparative, observer-blind trial enrolled healthy non-pregnant women 18–40 years of age. Women received a single dose of fully liquid (n = 529) or lyophilized (n = 521) trivalent GBS vaccine on day 1. Safety assessments were performed up to day 181 (study termination). Serotype Ia/Ib/III-specific immunoglobulin G (IgG) antibodies were measured in sera from women on day 1 (pre-vaccination) and day 31. Equivalence between the two formulations was demonstrated if the two-sided 95% confidence interval (CI) for the ratio (liquid/lyophilized) of the geometric mean concentrations (GMCs) on day 31 was contained in a (0.5, 2.0) interval for each serotype.

Results

Solicited and unsolicited adverse events were reported at similar rates for both formulations. Serious adverse events were reported for six (1.1%) liquid GBS and nine (1.7%) lyophilized GBS vaccinated women, none of which were considered related to vaccination or fatal. On day 31, serotype-specific IgG concentrations were 8–16-fold higher than on day 1 in both groups. Equivalence of the liquid to the lyophilized formulation 30 days post-vaccination was demonstrated as the 95% CIs of the GMC ratios were within the pre-specified interval for the three serotypes: GMC ratios were 1.02 (95% CI: 0.79, 1.32) for serotype Ia, 0.93 (0.71, 1.21) for serotype Ib and 0.99 (0.76, 1.30) for serotype III.

Conclusions

Both formulations of the investigational trivalent GBS vaccine had favorable safety profiles and induced similar GBS serotype-specific antibody concentrations. This study demonstrated that the fully liquid formulation was equivalent to the lyophilized formulation in healthy non-pregnant women in terms of immunogenicity for all three serotypes.

Clinical Trials Registration

NCT02270944.

中文翻译：

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研究性三价 B 组链球菌疫苗的全液体和冻干制剂在健康非孕妇中的安全性和免疫原性：随机比较 II 期试验的结果。

背景

我们评估了一种在研三价 B 群链球菌 (GBS) 疫苗的液体和冻干制剂在非孕妇中的安全性和免疫原性，并评估了这些制剂在血清型特异性免疫反应方面的等效性。

方法

这项 II 期、随机、比较、观察者盲试验招募了 18-40 岁的健康非孕妇。女性在第 1 天接受了单剂全液体 (n = 529) 或冻干 (n = 521) 三价 GBS 疫苗。安全性评估一直持续到第 181 天（研究终止）。在第 1 天（接种前）和第 31 天，在女性血清中测量了血清型 Ia/Ib/III 特异性免疫球蛋白 G (IgG) 抗体。如果两侧 95% 置信区间 (CI ) 第 31 天几何平均浓度 (GMC) 的比率（液体/冻干）包含在每个血清型的 (0.5, 2.0) 区间内。

结果

两种制剂的主动和主动不良事件报告率相似。6 名 (1.1%) 液体 GBS 和 9 名 (1.7%) 冻干 GBS 疫苗接种妇女报告了严重不良事件，其中没有一个被认为与疫苗接种有关或致命。在第 31 天，两组血清型特异性 IgG 浓度均比第 1 天高 8-16 倍。证明了疫苗接种后 30 天液体与冻干制剂的等效性，因为 GMC 比率的 95% CI 在三种血清型的预定区间内：GMC 比率为 1.02（95% CI：0.79，1.32）血清型 Ia，血清型 Ib 为 0.93 (0.71, 1.21)，血清型 III 为 0.99 (0.76, 1.30)。

结论

研究性三价 GBS 疫苗的两种配方都具有良好的安全性，并诱导相似的 GBS 血清型特异性抗体浓度。该研究表明，就所有三种血清型的免疫原性而言，全液体制剂与健康非孕妇中的冻干制剂相当。

临床试验注册

NCT02270944。