美国辉瑞公司Kena A. Swanson团队研究了成人呼吸道合胞病毒攻毒研究中的疫苗效力。这一研究成果发表在2022年6月22日出版的《新英格兰医学杂志》上。

虽然人类呼吸道合胞病毒（RSV）是老年人发病和死亡的重要原因，但尚未获得RSV疫苗许可。

在一项临床2a期研究中，研究组以1:1的比例随机分配健康成年人（18-50岁），分别接受单次肌肉注射二价融合前F（RSVpreF）疫苗或安慰剂。注射后大约28天，参与者通过鼻内接种RSV A孟菲斯37b攻击病毒，并观察12天。每个方案预先指定的主要终点如下：逆转录酶-定量聚合酶链反应（RT-qPCR）RSV感染确诊至少持续2天，且至少有两种类型中任何级别的临床症状或任何类型中至少有一种二级症状，从第1天到出院的总症状评分，以及病毒暴露到出院后第2天通过RT-qPCR测量的鼻腔冲洗液样本中RSV病毒载量的曲线下面积（AUC）。此外，研究组还评估了免疫原性和安全性。

参与者接种攻击病毒后，至少连续2天观察到任何可检测病毒RNA证实的症状性RSV感染的疫苗效力为86.7%。通过RT-qPCR测定，疫苗组RSV病毒载量（小时×log₁₀拷贝/毫升）的AUC中位数为0.0，安慰剂组为96.7。接种后28天，疫苗组RSV A中和滴度与基线相比几何平均因子增加20.5，安慰剂组为1.1。疫苗组比安慰剂组出现更多的局部注射部位疼痛。两组均未观察到严重不良事件。

研究结果表明，RSVpreF疫苗对症状性RSV感染和病毒脱落有效。未发现明显的安全问题。这些发现为在临床3期疗效研究中进一步评估RSVpreF疫苗提供了支持。

附：英文原文

Title: Vaccine Efficacy in Adults in a Respiratory Syncytial Virus Challenge Study

Author: Beate Schmoele-Thoma, M.D.,, Agnieszka M. Zareba, M.D., Ph.D.,, Qin Jiang, M.S.,, Mohan S. Maddur, D.V.M., Ph.D.,, Rana Danaf, M.Sc.,, Alex Mann, M.Sc.,, Kingsley Eze, B.Sc.,, Juin Fok-Seang, Ph.D.,, Golam Kabir, M.Sc.,, Andrew Catchpole, D.Phil.,, Daniel A. Scott, M.D.,, Alejandra C. Gurtman, M.D.,, Kathrin U. Jansen, Ph.D.,, William C. Gruber, M.D.,, Philip R. Dormitzer, M.D., Ph.D.,, and Kena A. Swanson, Ph.D.

Issue&Volume: 2022-06-22

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×log10 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.

DOI: 10.1056/NEJMoa2116154

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2116154