埃森和萨格勒布狂犬病PEP方案后冻干纯化人二倍体细胞狂犬病疫苗的安全性、免疫原性和免疫持久性：一项随机、盲法对照3期试验，参与者为10-60岁的健康参与者

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-04-05 DOI:10.1016/j.vaccine.2025.127082

Guifan Li , Shouchun Cao , Bidan Xu , Jialei Hu , Lei Zhang , Leitai Shi , Danhua Zhao , Yixin Li , Yafei Liu , Qi Liang , Xiaohong Wu

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引用次数: 0

摘要

目的评价冻干纯化人二倍体细胞狂犬病疫苗在健康人群和未接种狂犬病疫苗人群中的安全性、免疫原性和免疫持久性，采用传统的5剂量Essen方案和缩短的4剂量Zagreb方案进行狂犬病暴露后模拟预防。方法将1800名10 ~ 60岁健康受试者按1:1:1的比例随机分为5剂量试验组（T5、Essen方案）、5剂量对照组（C5、Essen方案）和4剂量试验组（T4、Zagreb方案），分别接种试验疫苗和对照疫苗，分析疫苗安全性及接种前后狂犬病抗体水平。结果不良反应主要发生在初始免疫剂量后，严重程度以轻度（1级）为主。T4组总不良事件发生率（38%）低于C5组总不良事件发生率（45%）（P = 0.02）；T5发热率（12%,P = 0.01）、T4发热率（13%,P = 0.03）低于C5发热率（17%）。未观察到与疫苗相关的严重不良反应（sae）。在第一次给药后14天，三组血清转换率均达到100%。T5、C5和T4首次接种后12个月血清转换率分别为98%、96%和98%。T5和T4在第一次给药后第7天、第14天、第12个月以及最后一次给药后第14天的中和抗体几何平均浓度（GMC）和几何平均增加量（GMI）均高于C5。T5与T4组ae发生率、血清转化率、GMC、GMI差异无统计学意义。结论采用Essen方案和Zagreb方案接种的试验疫苗具有良好的安全性、免疫原性和免疫持久性，不逊于对照疫苗。临床试验注册：NCT03971370。

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Safety, immunogenicity and immune persistence of a lyophilized purified human diploid cells rabies vaccine following rabies PEP regimen Essen and Zagreb: A randomized, blinded controlled phase 3 trial in healthy participants aged 10–60 years old

Objective

To evaluate the safety, immunogenicity and immune persistence of a lyophilized purified human diploid cells rabies vaccine in healthy and previously unvaccinated people in a simulated rabies post-exposure prophylaxis, by traditional 5-dose Essen regimen and abbreviated 4-dose Zagreb regimen.

Methods

A cohort of 1800 healthy participants aged 10–60 years old were randomized into three groups: 5-dose test group (T5, Essen regimen), 5-dose control group (C5, Essen regimen) and 4-dose test group (T4, Zagreb regimen) according to the ratio of 1:1:1, and inoculated with trial vaccine or control vaccine separately to analyze the safety of vaccine as well as rabies antibody levels before and after vaccination.

Results

Adverse reactions (AEs) mainly occurred after the initial dose of immunization, which were mostly mild (grade 1) in severity. The incidence of total AEs in T4 (38 %) was lower than that in C5 (45 %) (P = 0.02) from the initial dose to 28 days after the final dose; fever rate in T5 (12 %, P = 0.01) and T4 (13 %, P = 0.03) was lower than that in C5 (17 %). No vaccine-related serious AEs (SAEs) were observed. Seroconversion rates reached 100 % in all three groups 14 days following the first dose. Moreover, the seroconversion rate was 98 %, 96 % and 98 % 12 months following the first dose in T5, C5 and T4, respectively. Both T5 and T4 displayed higher neutralizing antibodies geometric mean concentration (GMC) and geometric mean increase (GMI) compared to those in C5 on day 7, day 14, and 12 months after the first dose, as well as on day 14 after the last dose. There were no significant differences in the incidence of AEs, seroconversion rate, GMC and GMI between T5 and T4.

Conclusion

The trial vaccine administered following both Essen regimen and Zagreb regimen shows good safety, immunogenicity and immune persistence, and the trial vaccine is not inferior to the control vaccine.

Clinical Trials Registration: NCT03971370.

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来源期刊

Vaccine 医学-免疫学

CiteScore

8.70

自引率

5.50%

发文量

992

审稿时长

131 days

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