EMI Editor’s Choice
Bilingual summaries: Safety, tolerability and immunogenicity of a quadrivalent recombinant norovirus vaccine (Pichia pastoris) in participants six weeks of age or older: Phase I/IIa trial
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中文简述：
诺如病毒是引发人类流行性急性胃肠炎和食源性腹泻病的主要病原体，开发安全有效的诺如病毒疫苗势在必行。安徽智飞龙科马生物制药有限公司研发的诺如病毒疫苗涵盖GI.1、GⅡ.3、GⅡ.4和GⅡ.17四种基因型，该疫苗已在中国广西壮族自治区完成一项随机、双盲、多队列、安慰剂对照Ⅰ/Ⅱa期临床试验，并由中国食品药品检定研究院完成临床样本的检验、指导免疫原性数据分析。试验结果显示，该候选疫苗表现出良好的免疫原性和安全性。
I/Ⅱa期临床试验结果显示，受试者在完成3剂次疫苗接种后30天，试验疫苗组在所有四种基因型（GI.1、GⅡ.3、GⅡ.4和GⅡ.17）中诱导的HBGA阻断抗体血清转化率和GMT均显著高于安慰剂组，表明该候选疫苗在6周龄及以上人群中接种后可诱导良好的免疫原性。
在剂量比较方面，高剂量组（25μg/型/剂）在四种基因型中诱导的HBGA阻断抗体血清转化率和GMT均高于低剂量组（12.5μg/型/剂）。同时，IgA和IgG抗体血清转化率及GMC也普遍呈现出高剂量组更高的趋势，与HBGA阻断抗体结果一致，共同提示高剂量组疫苗具有更好的免疫原性。
本研究还深入分析了血清中IgA、IgG和HBGA阻断抗体之间的相互关系，不论在高、低剂量组中，四种基因型的IgG-HBGA相关系数均高于IgA-HBGA相关系数，提示血清HBGA阻断抗体和IgG抗体之间存在着较强的相关性。
在安全性方面，该候选疫苗的不良反应主要发生于接种后0-7天内，且严重程度以1-2级为主。最常见的不良反应为发热，其次为腹泻。不良事件发生率未呈现剂量依赖性增加，高、低剂量组间无显著统计学差异，与安慰剂组相比，试验疫苗组未表现出新的安全性信号。
综上，Ⅰ/Ⅱa期临床试验表明，该候选诺如疫苗具有良好的安全性，及表现出令人满意的免疫原性，特别是婴幼儿。目前这款四价诺如疫苗已进入更加关键的Ⅲ期临床试验阶段，旨在更大规模人群中进一步验证其保护效力和安全性。
临床试验研究由安徽智飞龙科马生物制药有限公司、广西壮族自治区疾病预防控制中心、中国食品药品检定研究院共同完成，陈钢（安徽智飞龙科马生物制药有限公司）为本论文的第一作者，施礼威（广西壮族自治区疾病预防控制中心）、于晴川（中国食品药品检定研究院）、刘庆伟（重庆华智生物制药有限公司）为本论文共同第一作者。黄忠（复旦大学上海市重大传染病和生物安全研究院）、李静静（安徽智飞龙科马生物制药有限公司）、胡忠玉（中国食品药品检定研究院）、黄腾（广西壮族自治区疾病预防控制中心）为本论文共同通讯作者。
英文简述：
Norovirus is a leading cause of epidemic acute gastroenteritis and foodborne diarrheal disease in humans, making the development of safe and effective norovirus vaccines imperative. A norovirus vaccine developed by Anhui Zhifei Longcom Biopharmaceutical Co. Ltd., covering four genotypes (GI.1, GII.3, GII.4, and GII.17), has completed a randomized, double-blind, multi-cohort, placebo-controlled Phase I/IIa clinical trial in Guangxi Zhuang Autonomous Region, China. The National Institutes for Food and Drug Control (NIFDC) performed the clinical sample testing and guided the immunogenicity data analysis. The results demonstrated that the candidate vaccine exhibited favorable immunogenicity and safety.
Results from the Phase I/IIa clinical trial showed that 30 days after the completion of the three-dose vaccination schedule, the serum conversion rates of HBGA-blocking antibodies and GMTs induced by the vaccine for all four genotypes (GI.1, GII.3, GII.4, and GII.17) were significantly higher than the placebo. This indicates that the candidate vaccine can induce a robust immunogenic response in individuals aged 6 weeks and above.
In terms of dose comparison, the high-dose group (25 μg/genotype/dose) elicited higher HBGA-blocking antibody serum conversion rates and GMTs for all four genotypes compared to the low-dose group (12.5 μg/genotype/dose). Similarly, serum conversion rates and GMCs of IgA and IgG antibodies generally showed a trend toward higher values in the high-dose group, consistent with the HBGA-blocking antibody results. These findings collectively suggest that the high-dose formulation possesses superior immunogenicity.
This study also conducted an in-depth analysis of the correlations among serum IgA, IgG, and HBGA-blocking antibodies. In both the high- and low-dose groups, the correlation coefficients between IgG and HBGA-blocking antibodies were higher than those between IgA and HBGA-blocking antibodies across all four genotypes, indicating a stronger correlation between serum HBGA-blocking antibodies and IgG antibodies.
Regarding safety, adverse reactions to the candidate vaccine primarily occurred within 0–7 days after vaccination and were Grade 1–2 in severity. The most common adverse reactions were fever and diarrhea. The incidence of adverse events did not increase in a dose-dependent manner, and no statistically significant differences were observed between the high- and low-dose groups. Compared with the placebo group, the experimental vaccine group did not exhibit any new safety signals.
In conclusion, the Phase I/IIa clinical trial demonstrated that this candidate norovirus vaccine has a favorable safety profile and satisfactory immunogenicity, particularly in infants and young children. This quadrivalent recombinant norovirus vaccine has now progressed to a more critical Phase III clinical trial stage, aiming to further validate its protective efficacy and safety in a larger population.
The clinical trial study was jointly conducted by Anhui Zhifei Longcom Biopharmaceutical Co. Ltd., the Guangxi Zhuang Autonomous Region Disease Control and Prevention Center, and the National Institutes for Food and Drug Control (NIFDC) . Gang Chen (Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.) served as the first author of this paper. Liwei Shi (Guangxi Zhuang Autonomous Region Disease Control and Prevention Center), Qingchuan Yu (National Institutes for Food and Drug Control), and Qingwei Liu (Chongqing Huazhi Biopharmaceutical Co., Ltd.) were co-first authors. Zhong Huang (Shanghai Institute of Infectious Disease and Biosecurity, Shanghai Medical College, Fudan University), Jingjing Li (Anhui Zhifei Longcom Biopharmaceutical Co. Ltd.), Zhongyu Hu (National Institutes for Food and Drug Control), and Teng Huang (Guangxi Zhuang Autonomous Region Disease Control and Prevention Center) were co-corresponding authors of this paper.