Efficacy, Immunogenicity, and Safety of an Investigational Maternal Respiratory Syncytial Virus Prefusion F Protein-Based Vaccine.

IF 7.3 1区医学 Q1 IMMUNOLOGY Clinical Infectious Diseases Pub Date : 2026-02-09 DOI:10.1093/cid/ciaf033

Peyman Banooni, Bernard Gonik, Cristina Epalza, Osvaldo Reyes, Shabir A Madhi, Grace Devota Gomez-Go, Khalequ Zaman, Conrado Juan Llapur, Eduardo López-Medina, Thorsten Stanley, Anu Kantele, Li-Min Huang, Marisa Márcia Mussi-Pinhata, Jonas Dewulf, Joanne M Langley, Claudia Seidl, Martin Ota, Martha Kirabo, Bruno Anspach, Ilse Dieussaert, Ouzama Henry, Joon Hyung Kim, Marta Picciolato

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Abstract

Background: In this phase 3 trial of an investigational maternal respiratory syncytial virus prefusion F protein-based vaccine (RSVPreF3-Mat), a higher rate of preterm birth was observed in the vaccine (6.8%) versus the placebo group (4.9%). Trial enrollment and vaccination were stopped. Results of investigations into this safety signal were reported previously. Here, we describe end-of-trial efficacy, immunogenicity, and safety results.

Methods: Women 18-49 years old were randomized 2:1 to receive 1 dose of RSVPreF3-Mat (n = 3557) or placebo (n = 1771) at 240/7-340/7 weeks' gestation. Primary outcomes were any and severe medically assessed RSV-associated lower respiratory tract disease (MA-RSV-LRTD) in infants until 6 months postbirth and safety until 12 months postbirth. Other efficacy outcomes were evaluated, along with immunogenicity (until 6 months postpartum/birth) and safety in mothers and infants.

Results: Efficacy (with 95% credible interval) in infants until 6 months postbirth was 65.5% (37.5%-82.0%) against any MA-RSV-LRTD, 69.0% (33.0%-87.6%) against severe MA-RSV-LRTD, and 50.1% (-3.6% to 75.8%) against RSV hospitalization; it waned over time thereafter. Efficacy against MA-RSV-LRTD was 47.8% (-25.8% to 77.3%) in low- and middle-income and 75.9% (46.1%-91.5%) in high-income countries. RSVPreF3-Mat induced a substantial increase in RSV-A neutralization titers in mothers, with efficient transplacental transfer of antibodies that persisted in infants until at least 6 months postbirth.

Conclusions: Consistent with the high titers of transplacentally transferred antibodies, this trial suggests a reduced risk of any/severe MA-RSV-LRTD and RSV hospitalization until 6 months postbirth in infants born to mothers immunized with RSVPreF3-Mat during pregnancy. However, vaccine development was terminated due to an identified preterm birth risk. Clinical Trials Registration. NCT04605159.

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基于母体呼吸道合胞病毒F蛋白预融合疫苗的有效性、免疫原性和安全性

背景：在这项基于母体呼吸道合胞病毒预融合F蛋白疫苗（RSVPreF3-Mat）的3期临床试验中，该疫苗的早产率（6.8%）高于安慰剂组（4.9%）。试验登记和疫苗接种停止。对这一安全信号的调查结果已在之前报道过。在这里，我们描述了试验结束时的疗效、免疫原性和安全性结果。方法：18-49岁的女性以2:1的比例随机分配，在妊娠240/7-340/7周时接受一剂RSVPreF3-Mat （n=3557）或安慰剂（n=1771）。主要结局是婴儿出生后6个月前医学评估的任何和严重rsv相关下呼吸道疾病（MA-RSV-LRTD）和出生后12个月前的安全性。对其他疗效结果进行了评估，包括免疫原性（直到产后6个月）和母婴安全性。结果：婴儿出生后6个月对任何MA-RSV-LRTD的疗效为65.5%(95%可信区间：37.5-82.0)，对严重MA-RSV-LRTD的疗效为69.0%(33.0-87.6)，对RSV住院治疗的疗效为50.1% (-3.6-75.8)；此后，随着时间的推移，它逐渐减弱。在低收入和中等收入国家，对MA-RSV-LRTD的疗效为47.8%(-25.8-77.3)，在高收入国家为75.9%（46.1-91.5）。RSVPreF3-Mat诱导母亲体内RSV-A中和滴度大幅增加，婴儿体内抗体的有效经胎盘转移持续到出生后至少6个月。结论：与经胎盘转移抗体的高滴度一致，该试验表明，在怀孕期间接种RSVPreF3-Mat疫苗的母亲所生的婴儿在出生后6个月前发生任何/严重的MA-RSV-LRTD和RSV住院的风险降低。然而，由于确定存在早产风险，疫苗开发被终止。试验注册：ClinicalTrials.gov: NCT04605159。

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来源期刊

Clinical Infectious Diseases 医学-传染病学

CiteScore

25.00

自引率

2.50%

发文量

900

审稿时长

3 months

期刊介绍： Clinical Infectious Diseases (CID) is dedicated to publishing original research, reviews, guidelines, and perspectives with the potential to reshape clinical practice, providing clinicians with valuable insights for patient care. CID comprehensively addresses the clinical presentation, diagnosis, treatment, and prevention of a wide spectrum of infectious diseases. The journal places a high priority on the assessment of current and innovative treatments, microbiology, immunology, and policies, ensuring relevance to patient care in its commitment to advancing the field of infectious diseases.