MF59 佐剂、细胞培养来源的 A/H5N1、亚单位流感病毒疫苗的安全性、耐受性和免疫原性：在健康儿科受试者中进行的剂量发现临床试验结果。

Safety, Tolerability and Immunogenicity of an MF59-adjuvanted, Cell Culture-derived, A/H5N1, Subunit Influenza Virus Vaccine: Results From a Dose-finding Clinical Trial in Healthy Pediatric Subjects.

机构信息

From the Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.

Saint Louis University, St. Louis, Missouri.

出版信息

Pediatr Infect Dis J. 2019 Jul;38(7):757-764. doi: 10.1097/INF.0000000000002345.

DOI:10.1097/INF.0000000000002345

PMID:31194712

Abstract

BACKGROUND

A/H5N1 influenza virus has significant pandemic potential, and vaccination is the main prophylactic measure. This phase 2, randomized, observer-blind, multicenter study evaluated the safety and immunogenicity of two MF59-adjuvanted, cell culture-derived H5N1 (aH5N1c) vaccine formulations in healthy pediatric subjects 6 months to 17 years old.

METHODS

Subjects (N = 662) received 2 aH5N1c doses 3 weeks apart, containing either 7.5 μg (full dose) or 3.75 μg (half dose) hemagglutinin antigen per dose. Local reactions and adverse events (AEs) were assessed by age. Antibody responses were measured by hemagglutination inhibition assay and assessed as geometric mean titers, geometric mean ratios (GMRs) and percentages of subjects achieving titers ≥1:40 and seroconversion (NCT01776554).

RESULTS

No vaccine-related serious AEs occurred. Incidence of solicited local reactions and systemic AEs were similar across vaccine groups. Tenderness and irritability in <6-year olds, and injection site pain, myalgia and fatigue in 6-17-year olds were the most commonly reported reactions in both full- and half-dose recipients. Frequencies of AEs were lower after the second dose than the first dose in all vaccine and age groups. Three weeks after the administration of a second dose, both full- and half-dose formulations met the Center for Biologics Evaluation Research and Review (United States) and Committee for Medicinal Products for Human Use (EU) licensure criteria for titers ≥1:40 (full dose 96% subjects; half dose 86%), seroconversion (full dose 96% subjects; half dose 86%), and GMR (full dose GMR 262; half dose 84). Antibody responses were highest in 6-35-month olds.

CONCLUSIONS

In pediatric subjects, both aH5N1c vaccine formulations were well tolerated and highly immunogenic, meeting both US and EU licensure criteria for pandemic influenza vaccines.

摘要

背景

A/H5N1 流感病毒具有显著的大流行潜力，疫苗接种是主要的预防措施。本项 2 期、随机、观察者盲法、多中心研究评估了两种 MF59 佐剂、细胞培养衍生的 H5N1（aH5N1c）疫苗制剂在 6 个月至 17 岁健康儿科受试者中的安全性和免疫原性。

方法

受试者（N=662）每 3 周接受 2 剂 aH5N1c 疫苗，每剂含 7.5 μg（全剂量）或 3.75 μg（半剂量）血凝素抗原。根据年龄评估局部反应和不良事件（AE）。通过血凝抑制试验测量抗体反应，并评估为几何平均滴度、几何平均比（GMR）和达到滴度≥1:40 和血清转化率的受试者百分比（NCT01776554）。

结果

未发生与疫苗相关的严重 AE。各疫苗组的局部和全身 AE 发生率相似。在<6 岁儿童中，最常见的反应是触痛和易激惹，而在 6-17 岁儿童中，最常见的反应是注射部位疼痛、肌痛和疲劳。在所有疫苗和年龄组中，第二次给药后的 AE 频率均低于第一次给药。在第二次给药后 3 周，全剂量和半剂量制剂均符合美国生物制品评价与研究中心和欧盟人用药品委员会的许可标准，即滴度≥1:40（全剂量 96%的受试者；半剂量 86%）、血清转化率（全剂量 96%的受试者；半剂量 86%）和 GMR（全剂量 GMR 262；半剂量 84）。抗体反应在 6-35 月龄儿童中最高。