呼吸道合胞病毒挑战研究中成人的疫苗效力。

Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study.

机构信息

From Vaccine Research and Development, Pfizer Pharma, Berlin (B.S.-T.); Vaccine Research and Development, Pfizer, Collegeville, PA (A.M.Z., Q.J., D.A.S.); Vaccine Research and Development, Pfizer, Pearl River, NY (M.S.M., A.C.G., K.U.J., W.C.G., P.R.D., K.A.S.); and hVIVO, London (R.D., A.M., K.E., J.F.-S., G.K., A.C.).

出版信息

N Engl J Med. 2022 Jun 23;386(25):2377-2386. doi: 10.1056/NEJMoa2116154.

DOI:10.1056/NEJMoa2116154

PMID:35731653

Abstract

BACKGROUND

Although human respiratory syncytial virus (RSV) is an important cause of illness and death in older adults, no RSV vaccine has been licensed.

METHODS

In a phase 2a study, we randomly assigned healthy adults (18 to 50 years of age), in a 1:1 ratio, to receive a single intramuscular injection of either bivalent prefusion F (RSVpreF) vaccine or placebo. Approximately 28 days after injection, participants were inoculated intranasally with the RSV A Memphis 37b challenge virus and observed for 12 days. The per-protocol prespecified primary end points were the following: reverse-transcriptase-quantitative polymerase-chain-reaction (RT-qPCR)-confirmed detectable RSV infection on at least 2 consecutive days with at least one clinical symptom of any grade from two categories or at least one grade 2 symptom from any category, the total symptom score from day 1 to discharge, and the area under the curve (AUC) for the RSV viral load in nasal-wash samples measured by means of RT-qPCR from day 2 after challenge to discharge. In addition, we assessed immunogenicity and safety.

RESULTS

After participants were inoculated with the challenge virus, vaccine efficacy of 86.7% (95% CI, 53.8 to 96.5) was observed for symptomatic RSV infection confirmed by any detectable viral RNA on at least 2 consecutive days. The median AUC for the RSV viral load (hours × log copies per milliliter) as measured by RT-qPCR assay was 0.0 (interquartile range, 0.0 to 19.0) in the vaccine group and 96.7 (interquartile range, 0.0 to 675.3) in the placebo group. The geometric mean factor increase from baseline in RSV A-neutralizing titers 28 days after injection was 20.5 (95% CI, 16.6 to 25.3) in the vaccine group and 1.1 (95% CI, 0.9 to 1.3) in the placebo group. More local injection-site pain was noted in the vaccine group than in the placebo group. No serious adverse events were observed in either group.

CONCLUSIONS

RSVpreF vaccine was effective against symptomatic RSV infection and viral shedding. No evident safety concerns were identified. These findings provide support for further evaluation of RSVpreF vaccine in a phase 3 efficacy study. (Funded by Pfizer; EudraCT number, 2020-003887-21; ClinicalTrials.gov number, NCT04785612.).

摘要

背景

虽然人类呼吸道合胞病毒（RSV）是导致老年人发病和死亡的重要原因，但尚未有 RSV 疫苗获得许可。

方法

在一项 2a 期研究中，我们以 1:1 的比例随机分配健康成年人（18 至 50 岁），接受单剂量肌肉内注射二价融合前 F（RSVpreF）疫苗或安慰剂。大约在注射后 28 天，参与者接受 RSV A Memphis 37b 挑战病毒的鼻内接种，并观察 12 天。按方案规定的主要终点如下：至少连续 2 天至少有两个类别之一的任何等级的至少一个临床症状或任何类别之一的至少一个 2 级症状，并且至少有一个症状等级为 2 级，从第 1 天到出院的总症状评分，以及从挑战后第 2 天到出院通过逆转录-定量聚合酶链反应（RT-qPCR）测量鼻洗液样本中 RSV 病毒载量的曲线下面积（AUC）。此外，我们评估了免疫原性和安全性。

结果

在参与者接种挑战病毒后，观察到疫苗对任何连续 2 天以上至少有一个临床症状且至少有两个类别之一的任何等级或任何类别之一的至少一个 2 级症状的 RSV 感染的有效性为 86.7%（95%CI，53.8 至 96.5）。通过 RT-qPCR 测定，病毒载量（小时×log 拷贝/毫升）的 RSV AUC 中位数在疫苗组中为 0.0（四分位距，0.0 至 19.0），在安慰剂组中为 96.7（四分位距，0.0 至 675.3）。注射后 28 天，RSV A 中和滴度与基线相比的几何平均倍数增加在疫苗组中为 20.5（95%CI，16.6 至 25.3），在安慰剂组中为 1.1（95%CI，0.9 至 1.3）。与安慰剂组相比，疫苗组更多地出现局部注射部位疼痛。两组均未观察到严重不良事件。