比利时葛兰素史克Ilse Dieussaert团队研究了基于RSV预融合F蛋白的母体疫苗-早产和其他结局。相关论文于2024年3月13日发表在《新英格兰医学杂志》上。

孕期接种呼吸道合胞病毒疫苗可保护婴儿免受呼吸道合胞肺炎的侵袭。目前亟需一种候选的基于RSV预融合F蛋白的母体疫苗（RSVPreF3-Mat）的有效性和安全性数据。

研究组对18至49岁的孕妇进行了一项3期试验，以评估RSVPreF3 Mat的疗效和安全性。这些女性以2:1的比例随机分配，在妊娠24周0天至34周0天期间接受RSVPreF3 Mat或安慰剂治疗。主要结局是对出生至6个月大婴儿的任何或严重的呼吸道合胞病毒相关下呼吸道疾病以及出生至12个月大婴儿的安全性进行医学评估。在观察到疫苗组早产风险高于安慰剂组后，提前停止了登记和疫苗接种，并对早产的安全信号进行了探索性分析。

分析包括5328名孕妇和5233名婴儿；由于提前停止登记，约10000名孕妇及其婴儿的目标登记没有实现。研究组对疫苗组的3426名婴儿和安慰剂组的1711名婴儿进行了从出生到6个月大的随访；分别有16名和24名婴儿患有任何医学评估的呼吸道合胞病毒相关下呼吸道疾病（疫苗有效性，65.5%；95%可信区间，37.5至82.0），分别有8名和14名婴儿患有严重的医学评估的RSV相关下呼吸道疾病（疫苗有效率，69.0%；95%可信间隔，33.0至87.6）。

疫苗组中6.8%的婴儿（3494例中有237例）早产，安慰剂组4.9%的婴儿早产（1739例中有86例）（相对风险1.37；95%置信区间[CI]1.08-1.74；P=0.01）；新生儿死亡发生率分别为0.4%（3494例中有13例）和0.2%（1739例中有3例）（相对风险，2.16；95%可信区间，0.62至7.56；P=0.023），这种不平衡可能归因于疫苗组早产的比例更高。未观察到其他安全信号。

这项试验的结果表明，与安慰剂相比，候选母体呼吸道合胞病毒疫苗在婴儿中患任何和严重的医学评估的呼吸道合胞相关下呼吸道疾病的风险都较低，但候选疫苗的早产风险更高。

附：英文原文

Title: RSV Prefusion F Protein–Based Maternal Vaccine — Preterm Birth and Other Outcomes

Author: Ilse Dieussaert, Joon Hyung Kim, Sabine Luik, Claudia Seidl, Wenji Pu, Jens-Ulrich Stegmann, Geeta K. Swamy, Peggy Webster, Philip R. Dormitzer

Issue&Volume: 2024-03-13

Abstract:

Background

Vaccination against respiratory syncytial virus (RSV) during pregnancy may protect infants from RSV disease. Efficacy and safety data on a candidate RSV prefusion F protein–based maternal vaccine (RSVPreF3-Mat) are needed.

Methods

We conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. The women were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age. After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed.

Results

The analyses included 5328 pregnant women and 5233 infants; the target enrollment of approximately 10,000 pregnant women and their infants was not reached because enrollment was stopped early. A total of 3426 infants in the vaccine group and 1711 infants in the placebo group were followed from birth to 6 months of age; 16 and 24 infants, respectively, had any medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and 8 and 14, respectively, had severe medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6). Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P=0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P=0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group. No other safety signal was observed.

Conclusions

The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine.

DOI: 10.1056/NEJMoa2305478

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2305478