ABSTRACT

Objective

To evaluate the immunogenicity, safety and lot-to-lot consistency of an inactivated enterovirus 71 (EV71) vaccine cultured in bioreactors with different specifications after full immunization.

Methods

A randomized, double-blind trial was performed in 3,000 children aged 6 ~ 35 months with six vaccine batches, which were prepared in 40 L and 150 L bioreactors for three consecutive batches respectively. Children were immunized on day 0 and 28, serum samples were collected on day 0 and 56, and neutralizing antibody titers were determined by the microcytopathic method. Immediate reactions were recorded within 30 min, local and systemic symptoms were recorded within 0 ~ 28 days, and serious adverse events were recorded within 6 months.

Results

After immunization with two doses of the inactivated EV71 vaccine, the neutralizing antibody GMT was 825.52 ± 4.09, and the positive conversion rate was 96.18%, with no significant difference. The 95% CI of the serum neutralizing antibody GMT ratio between the two groups after immunization with the three vaccine batches produced in the 150 L and 40 L bioreactors ranged from .67 ~ 1.5. The overall incidence of adverse reactions, mainly grade 1 reactions, for all 6 batches from 0 to 28 days after vaccination was 49.62%, with no significant difference (p = .8736). The incidence of systemic adverse reactions, primarily fever and diarrhea, was 45.14%; the incidence of local adverse reactions, primarily erythema and tenderness, was 9.43%.

Conclusion

The EV71 vaccine was highly immunogenic and safe in children aged 6–35 months, and 6 consecutive batches produced by the two bioreactors with different specifications were consistent.

中文翻译：

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商业规模 IV 期临床试验中肠道病毒 71 疫苗批次间一致性的临床评价

摘要

客观的

评价肠道病毒71型（EV71）灭活疫苗在不同规格生物反应器中全免后的免​​疫原性、安全性和批间一致性。

方法

在 3,000 名 6 ~ 35 个月大的儿童中进行了一项随机双盲试验，分六个批次分别在 40 L 和 150 L 生物反应器中制备连续三个批次的疫苗。在第 0 天和第 28 天对儿童进行免疫，在第 0 天和第 56 天收集血清样本，并通过微细胞病变法测定中和抗体滴度。30分钟内记录即时反应，0～28天记录局部和全身症状，6个月内记录严重不良事件。

结果

两剂EV71灭活疫苗免疫后，中和抗体GMT为825.52±4.09，阳转率为96.18%，无显着差异。150L和40L生物反应器生产的三批疫苗免疫后两组间血清中和抗体GMT比值的95%CI为0.67~1.5。接种后 0 至 28 天的所有 6 个批次的不良反应总发生率为 49.62%，主要是 1 级反应，无显着差异 (p = .8736)。以发热、腹泻为主的全身不良反应发生率为45.14%；以红斑和压痛为主的局部不良反应发生率为9.43%。

结论

EV71疫苗在6-35月龄儿童中具有高免疫原性和安全性，两个不同规格的生物反应器生产的连续6批次产品一致。