Ad26.RSV.preF-RSV 预 F 蛋白疫苗在老年人中的疗效和安全性。

Efficacy and Safety of an Ad26.RSV.preF-RSV preF Protein Vaccine in Older Adults.

机构信息

From the University of Rochester School of Medicine, Rochester, NY (A.R.F.); Janssen Vaccines and Prevention, Leiden, the Netherlands (K.W., A.R.B., J.S., M.D., B.C., C.A.C., E.H.); Janssen Infectious Diseases, Beerse, Belgium (E.G., J.M., E.D.P., S.V.); Trial Professionals Consultant Group, Woodstock, MD (S.B.); AMR Kansas City, Kansas City, MO (J.E.); and Janssen Global Services, Raritan, NJ (E.K.H.C.).

出版信息

N Engl J Med. 2023 Feb 16;388(7):609-620. doi: 10.1056/NEJMoa2207566.

DOI:10.1056/NEJMoa2207566

PMID:36791161

Abstract

BACKGROUND

Respiratory syncytial virus (RSV) can cause serious lower respiratory tract disease in older adults, but no licensed RSV vaccine currently exists. An adenovirus serotype 26 RSV vector encoding a prefusion F (preF) protein (Ad26.RSV.preF) in combination with RSV preF protein was previously shown to elicit humoral and cellular immunogenicity.

METHODS

We conducted a randomized, double-blind, placebo-controlled, phase 2b, proof-of-concept trial to evaluate the efficacy, immunogenicity, and safety of an Ad26.RSV.preF-RSV preF protein vaccine. Adults who were 65 years of age or older were randomly assigned in a 1:1 ratio to receive vaccine or placebo. The primary end point was the first occurrence of RSV-mediated lower respiratory tract disease that met one of three case definitions: three or more symptoms of lower respiratory tract infection (definition 1), two or more symptoms of lower respiratory tract infection (definition 2), and either two or more symptoms of lower respiratory tract infection or one or more symptoms of lower respiratory tract infection plus at least one systemic symptom (definition 3).

RESULTS

Overall, 5782 participants were enrolled and received an injection. RSV-mediated lower respiratory tract disease meeting case definitions 1, 2, and 3 occurred in 6, 10, and 13 vaccine recipients and in 30, 40, and 43 placebo recipients, respectively. Vaccine efficacy was 80.0% (94.2% confidence interval [CI], 52.2 to 92.9), 75.0% (94.2% CI, 50.1 to 88.5), and 69.8% (94.2% CI, 43.7 to 84.7) for case definitions 1, 2, and 3, respectively. After vaccination, RSV A2 neutralizing antibody titers increased by a factor of 12.1 from baseline to day 15, a finding consistent with other immunogenicity measures. Percentages of participants with solicited local and systemic adverse events were higher in the vaccine group than in the placebo group (local, 37.9% vs. 8.4%; systemic, 41.4% vs. 16.4%); most adverse events were mild to moderate in severity. The frequency of serious adverse events was similar in the vaccine group and the placebo group (4.6% and 4.7%, respectively).

CONCLUSIONS

In adults 65 years of age or older, Ad26.RSV.preF-RSV preF protein vaccine was immunogenic and prevented RSV-mediated lower respiratory tract disease. (Funded by Janssen Vaccines and Prevention; CYPRESS ClinicalTrials.gov number, NCT03982199.).

摘要

背景

呼吸道合胞病毒（RSV）可导致老年人下呼吸道严重疾病，但目前尚无获得许可的 RSV 疫苗。先前已证明，腺病毒血清型 26 RSV 载体编码融合前 F（preF）蛋白（Ad26.RSV.preF）与 RSV preF 蛋白联合可引发体液和细胞免疫原性。

方法

我们开展了一项随机、双盲、安慰剂对照、2b 期概念验证试验，以评估 Ad26.RSV.preF-RSV preF 蛋白疫苗的疗效、免疫原性和安全性。65 岁或以上的成年人按 1:1 比例随机分配接受疫苗或安慰剂。主要终点为符合以下三种下呼吸道疾病定义之一的 RSV 介导的下呼吸道疾病首次发生：下呼吸道感染三个或更多症状（定义 1）、下呼吸道感染两个或更多症状（定义 2）或下呼吸道感染两个或更多症状或下呼吸道感染一个或更多症状加至少一个全身症状（定义 3）。

结果

总体而言，5782 名参与者入组并接受了注射。符合定义 1、2 和 3 的 RSV 介导的下呼吸道疾病分别在 6、10 和 13 名疫苗接种者和 30、40 和 43 名安慰剂接种者中发生。疫苗效力分别为 80.0%（94.2%置信区间[CI]，52.2 至 92.9）、75.0%（94.2%CI，50.1 至 88.5）和 69.8%（94.2%CI，43.7 至 84.7）。接种疫苗后，从基线到第 15 天，RSV A2 中和抗体滴度增加了 12.1 倍，这与其他免疫原性测量结果一致。与安慰剂组相比，疫苗组报告的局部和全身不良事件的发生率更高（局部：37.9% vs. 8.4%；全身：41.4% vs. 16.4%）；大多数不良事件为轻度至中度严重程度。疫苗组和安慰剂组严重不良事件的频率相似（分别为 4.6%和 4.7%）。