美国Novavax公司Louis F. Fries团队研究了妊娠期接种呼吸道合胞体病毒疫苗对婴儿的影响。该成果于2020年7月30日发表在《新英格兰医学杂志》上。

呼吸道合胞病毒（RSV）是婴儿严重下呼吸道感染的主要原因，最严重的病例集中在更幼小的婴儿中。

研究组招募了4636名健康孕妇，妊娠28周0天至36周0天，预产期接近RSV季，将其按2：1随机分组，分别接受肌注单剂量RSV融合（F）蛋白纳米颗粒疫苗或安慰剂。婴儿出生后追踪180天来评估与下呼吸道感染相关的结局，随访1年来评估其安全性。

共有4579例婴儿活产。婴儿出生后的前90天，疫苗组和安慰剂组中RSV相关、医学上显著的下呼吸道感染的婴儿分别占1.5%和2.4%，疫苗效价为39.4%。疫苗组和安慰剂组中RSV相关下呼吸道感染伴严重低氧血症的婴儿分别占0.5%和1.0%，疫苗效价为48.3%；RSV相关下呼吸道感染住院率分别为2.1%和3.7%，疫苗效价为44.4%。疫苗组的女性局部注射部位反应发生率为40.7%，显著高于安慰剂组（9.9％），但两组中其他不良事件发生率相差不大。

总之，孕妇接种RSV-F蛋白纳米颗粒疫苗后，在90天以内的婴儿中，未能有效预防RSV相关的医学上显著的下呼吸道感染。

附：英文原文

Title: Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants

Author: Shabir A. Madhi, M.B., Ch.B., F.C.Paed.(SA), Ph.D.,, Fernando P. Polack, M.D.,, Pedro A. Piedra, M.D.,, Flor M. Munoz, M.D.,, Adrian A. Trenholme, M.B., F.R.A.C.P.,, Eric A.F. Simes, M.D.,, Geeta K. Swamy, M.D.,, Sapeckshita Agrawal, Ph.D., M.S.P.H.,, Khatija Ahmed, M.D.,, Allison August, M.D.,, Abdullah H. Baqui, M.B., B.S., Dr.P.H.,, Anna Calvert, M.B., Ch.B.,, Janice Chen, M.S.,, Iksung Cho, M.S.,, Mark F. Cotton, M.D., Ph.D.,, Clare L. Cutland, M.B., B.CH., Ph.D.,, Janet A. Englund, M.D.,, Amy Fix, M.S.,, Bernard Gonik, M.D.,, Laura Hammitt, M.D.,, Paul T. Heath, F.R.C.P.C.H.,, Joanne N. de Jesus, M.D.,, Christine E. Jones, M.R.C.P.C.H., Ph.D.,, Asma Khalil, M.D., M.R.C.O.G.,, David W. Kimberlin, M.D.,, Romina Libster, M.D.,, Conrado J. Llapur, M.D.,, Marilla Lucero, M.D., Ph.D.,, Gonzalo Pérez Marc, M.D.,, Helen S. Marshall, M.D.,, Masebole S. Masenya, M.D.,, Federico Martinón-Torres, M.D., Ph.D.,, Jennifer K. Meece, Ph.D.,, Terry M. Nolan, M.B., B.S., Ph.D.,, Ayman Osman, M.D.,, Kirsten P. Perrett, M.D., Ph.D.,, Joyce S. Plested, Ph.D.,, Peter C. Richmond, M.B., B.S., F.R.A.C.P.,, Matthew D. Snape, M.B., B.S., M.D.,, Julie H. Shakib, D.O.,, Vivek Shinde, M.D.,, Tanya Stoney, M.B., B.S.,, D. Nigel Thomas, Ph.D.,, Alan T. Tita, M.D., Ph.D.,, Michael W. Varner, M.D.,, Manu Vatish, D.Phil., F.R.C.O.G.,, Keith Vrbicky, M.D.,, Judy Wen, B.S.,, Khalequ Zaman, Ph.D.,, Heather J. Zar, M.D., Ph.D.,, Gregory M. Glenn, M.D.,, and Louis F. Fries, M.D.

Issue&Volume: 2020-07-29

Abstract: BACKGROUND

Respiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants.

METHODS

Healthy pregnant women, at 28 weeks 0 days through 36 weeks 0 days of gestation, with an expected delivery date near the start of the RSV season, were randomly assigned in an overall ratio of approximately 2:1 to receive a single intramuscular dose of RSV fusion (F) protein nanoparticle vaccine or placebo. Infants were followed for 180 days to assess outcomes related to lower respiratory tract infection and for 364 days to assess safety. The primary end point was RSV-associated, medically significant lower respiratory tract infection up to 90 days of life, and the primary analysis of vaccine efficacy against the primary end point was performed in the per-protocol population of infants (prespecified criterion for success, lower bound of the 97.52% confidence interval [CI] of ≥30%).

RESULTS

A total of 4636 women underwent randomization, and there were 4579 live births. During the first 90 days of life, the percentage of infants with RSV-associated, medically significant lower respiratory tract infection was 1.5% in the vaccine group and 2.4% in the placebo group (vaccine efficacy, 39.4%; 97.52% CI, 1.0 to 63.7; 95% CI, 5.3 to 61.2). The corresponding percentages for RSV-associated lower respiratory tract infection with severe hypoxemia were 0.5% and 1.0% (vaccine efficacy, 48.3%; 95% CI, 8.2 to 75.3), and the percentages for hospitalization for RSV-associated lower respiratory tract infection were 2.1% and 3.7% (vaccine efficacy, 44.4%; 95% CI, 19.6 to 61.5). Local injection-site reactions among the women were more common with vaccine than with placebo (40.7% vs. 9.9%), but the percentages of participants who had other adverse events were similar in the two groups.

CONCLUSIONS

RSV F protein nanoparticle vaccination in pregnant women did not meet the prespecified success criterion for efficacy against RSV-associated, medically significant lower respiratory tract infection in infants up to 90 days of life. The suggestion of a possible benefit with respect to other end-point events involving RSV-associated respiratory disease in infants warrants further study.

DOI: NJ202007303830510

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1908380