Sanofi Pasteur, 1 Discovery Dr, Swiftwater, PA 18370, USA.
Sanofi Pasteur, 1 Discovery Dr, Swiftwater, PA 18370, USA.
Vaccine. 2019 Sep 16;37(39):5825-5834. doi: 10.1016/j.vaccine.2019.08.016. Epub 2019 Aug 17.
BACKGROUND: A high-dose, split-virion inactivated trivalent influenza vaccine (IIV3-HD; Fluzone® High-Dose, Sanofi Pasteur) is available for adults ≥65 years of age. This study examined the safety and immunogenicity of a quadrivalent high-dose split-virion inactivated influenza vaccine (IIV4-HD). METHODS: This was a randomized, modified double-blind, active-controlled, multi-center trial in healthy adults ≥65 years of age. Subjects were randomized in a 4:1:1 ratio to receive a single intramuscular injection of IIV4-HD, the licensed IIV3-HD, or an IIV3-HD containing the alternate B-lineage strain. Hemagglutination inhibition (HAI), seroneutralisation, and anti-neuraminidase antibody titers were measured at baseline and day 28. Solicited reactions were collected for up to 7 days, unsolicited adverse events up to 28 days, and serious adverse events up to 180 days. The primary immunogenicity objective was to demonstrate that IIV4-HD induces HAI geometric mean titers (GMTs) and seroconversion rates that are non-inferior to those induced by IIV3-HD. Secondary objectives were to describe the safety of IIV4-HD and IIV3-HD and to demonstrate that IIV4-HD induces HAI GMTs and seroconversion rates that are superior to those induced by IIV3-HD not containing the same B-lineage strain. RESULTS: The study included 2670 adults ≥65 years of age. For all four strains, HAI GMTs and seroconversion rates induced by IIV4-HD were non-inferior to those induced by IIV3-HDs containing the same strains. For both B strains, HAI GMTs and seroconversion rates induced by IIV4-HD were superior to those induced by IIV3-HD not containing the same B-lineage strain. Seroneutralisation and anti-neuraminidase antibody responses, measured in a subset of subjects, were similar. No new safety concerns were identified, and the safety profiles of IIV4-HD and IIV3-HD were similar. CONCLUSIONS: Adding a second B strain in IIV4-HD resulted in improved immunogenicity against the added strain without compromising the immunogenicity of the other strains or the vaccine's tolerability. CLINICAL TRIAL REGISTRATION: NCT03282240.
背景：一种高剂量、分裂病毒灭活三价流感疫苗（IIV3-HD；Fluzone® High-Dose，赛诺菲巴斯德）可用于 65 岁及以上的成年人。本研究旨在评估一种四价高剂量分裂病毒灭活流感疫苗（IIV4-HD）的安全性和免疫原性。
方法：这是一项在健康 65 岁及以上成年人中进行的随机、改良的双盲、主动对照、多中心试验。受试者以 4:1:1 的比例随机接受单次肌肉注射 IIV4-HD、已上市的 IIV3-HD 或含有替代 B 谱系株的 IIV3-HD。在基线和第 28 天测量血凝抑制（HAI）、血清中和和抗神经氨酸酶抗体滴度。在最多 7 天内收集有症状反应，在最多 28 天内收集无症状不良事件，在最多 180 天内收集严重不良事件。主要免疫原性目标是证明 IIV4-HD 诱导的 HAI 几何平均滴度（GMT）和血清转化率不低于 IIV3-HD 诱导的 HAI 几何平均滴度和血清转化率。次要目标是描述 IIV4-HD 和 IIV3-HD 的安全性，并证明 IIV4-HD 诱导的 HAI GMT 和血清转化率优于不含有相同 B 谱系株的 IIV3-HD 诱导的 HAI GMT 和血清转化率。
结果：该研究纳入了 2670 名 65 岁及以上的成年人。对于所有四种菌株，IIV4-HD 诱导的 HAI GMT 和血清转化率均不劣于含有相同菌株的 IIV3-HD。对于两种 B 株，IIV4-HD 诱导的 HAI GMT 和血清转化率均优于不含有相同 B 谱系株的 IIV3-HD。在亚组受试者中测量的血清中和和抗神经氨酸酶抗体反应相似。未发现新的安全性问题，且 IIV4-HD 和 IIV3-HD 的安全性特征相似。
结论：在 IIV4-HD 中添加第二种 B 株可提高对添加株的免疫原性，同时不影响其他株的免疫原性或疫苗的耐受性。
临床试验注册：NCT03282240。
Hum Vaccin Immunother. 2017-11-17
Hum Vaccin Immunother. 2017-9-2
J Prev Med Hyg. 2025-4-15
Hum Vaccin Immunother. 2024-12-31
J Epidemiol Glob Health. 2024-9
Zotero 插件