Ad26/protein preF RSV 疫苗对患有或不患有严重呼吸道合胞病毒疾病高危合并症的 18 至 59 岁成人的安全性和免疫原性：3 期随机对照免疫桥接试验。

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2024-11-12 DOI:10.1016/j.vaccine.2024.126514

Archana Jastorff , Efi Gymnopoulou , Jose Salas , Elizabeth Merrall , Erik Buntinx , Charlotte Martin , Helena H. Askling , Isabelle Schenkenberger , Angela Cano Yuste , William Smith , Roberto Sotolongo , Charlotte Von Engelhardt , Arangassery Rosemary Bastian , Christy Comeaux , Nynke Ligtenberg , Benoit Callendret , Esther Heijnen

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引用次数: 0

摘要

背景：呼吸道合胞病毒（RSV）对患有慢性并发症的成年人造成了严重的疾病负担。与建议接种 RSV 疫苗的健康老年人相比，有风险因素的年轻成年人的 RSV 重症发病率和死亡率同样高，甚至更高。我们使用 Ad26/蛋白 RSV preF 疫苗进行了一项免疫桥接研究，该疫苗之前曾在年龄≥65 岁的成年人中证明了其疗效，以支持将在老年人群中证明的疗效外推至严重 RSV 疾病高风险的年轻成年人群：这项3期随机、双盲、安慰剂对照试验评估了Ad26/蛋白前F型RSV在18-59岁无慢性心脏或肺部合并症（队列1）和有慢性心脏或肺部合并症（队列2）的成人中的安全性/耐受性和免疫原性，并与对RSV疾病有疗效的≥65岁成人（队列3）进行了比较。在基线、第 15 天和第 183 天评估体液和细胞免疫反应。对所有参与者的反应生成性和安全性进行了评估：共有 1118 人参加了研究（群组 1：387 人；群组 2：388 人；群组 3：343 人）。与年龄≥65岁的成年人相比，18-59岁成年人（包括高危人群）的RSV中和抗体滴度并不劣于后者。疫苗接种后第 15 天，前 F A IgG 抗体水平和 RSV-F 特异性γ干扰素 T 细胞频率均有所上升，并且在所有组别中至少 6 个月内保持高于基线水平。反应生成性和安全性临床上可以接受，但与年龄有关，18-59 岁成人的 3 级全身不良反应发生率高于≥65 岁的成人：Ad26/protein preF RSV 疫苗可诱导 18-59 岁成年人产生强大的体液和细胞免疫反应，无论是否患有慢性心脏或肺部合并症，其程度与老年人的反应相似，因此可推断该人群对 RSV 相关呼吸道疾病的疗效和保护作用。

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Safety and immunogenicity of the Ad26/protein preF RSV vaccine in adults aged 18 to 59 years with and without at-risk comorbidities for severe respiratory syncytial virus disease: A phase 3, randomized, controlled, immunobridging trial

Background

Respiratory syncytial virus (RSV) causes a significant disease burden in adults with chronic comorbidities. Rates of severe RSV disease and death are as high, or higher in younger adults with risk factors than in healthy older adults in whom RSV vaccination is recommended. We conducted an immunobridging study using the Ad26/protein RSV preF vaccine, which previously demonstrated efficacy in adults aged ≥65 years to support extrapolation of efficacy demonstrated in an older population to younger adult populations at high risk of severe RSV disease.

Methods

This Phase 3 randomized, double-blind, placebo-controlled trial assessed the safety/tolerability and immunogenicity of Ad26/protein preF RSV in adults aged 18–59 years without (Cohort 1) and with (Cohort 2) chronic cardiac or pulmonary comorbidities, compared to adults aged ≥65 years (Cohort 3) in whom efficacy against RSV disease was demonstrated. Humoral and cellular immune responses were assessed at baseline, Days 15 and 183. Reactogenicity and safety were assessed in all participants.

Results

1118 participants were enrolled (Cohort 1: 387; Cohort 2: 388; Cohort 3: 343). Compared to adults aged ≥65 years RSV neutralizing antibody titers were non-inferior in adults aged 18–59 years, including those at high risk. Levels of pre-F A IgG antibodies and frequencies of RSV-F specific interferon-gamma T-cells increased by Day 15 post-vaccination, and remained above baseline for at least 6 months in all cohorts. Reactogenicity and safety were clinically acceptable but age-dependent, with higher rates of Grade 3 systemic adverse events in adults aged 18–59-years than adults ≥65 years.

Conclusion

Ad26/protein preF RSV vaccine induced robust humoral and cellular immune responses in adults aged 18–59 years with or without chronic cardiac or pulmonary comorbidities, of similar magnitude to responses in older adults, allowing inference of efficacy and protection against RSV-associated respiratory disease in this population. www.clinicaltrials.gov NCT05070546

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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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