Respiratory Syncytial Virus Vaccination during Pregnancy and Effects in Infants

被引：295

作者：

Madhi, S. A. ^{[1
,2
]}

Polack, F. P. ^{[7
]}

Piedra, P. A. ^{[11
,12
]}

Munoz, F. M. ^{[11
,12
]}

Trenholme, A. A. ^{[13
]}

Simoes, E. A. F. ^{[14
,15
]}

Swamy, G. K. ^{[16
]}

Agrawal, S. ^{[17
]}

Ahmed, K. ^{[4
]}

August, A. ^{[17
]}

Baqui, A. H. ^{[18
]}

Calvert, A. ^{[20
]}

Chen, J. ^{[17
]}

Cho, I. ^{[17
]}

Cotton, M. F. ^{[5
]}

Cutland, C. L. ^{[1
,2
]}

Englund, J. A. ^{[27
]}

Fix, A. ^{[17
]}

Gonik, B. ^{[28
]}

Hammitt, L. ^{[19
]}

Heath, P. T. ^{[20
]}

de Jesus, J. N. ^{[29
]}

Jones, C. E. ^{[22
,23
]}

Khalil, A. ^{[21
]}

Kimberlin, D. W. ^{[30
]}

Libster, R. ^{[7
,9
]}

Llapur, C. J. ^{[10
]}

Lucero, M. ^{[29
]}

Marc, G. Perez ^{[8
]}

Marshall, H. S. ^{[33
,34
]}

Masenya, M. S. ^{[3
]}

Martinon-Torres, F. ^{[39
]}

Meece, J. K. ^{[38
]}

Nolan, T. M. ^{[35
,36
]}

Osman, A. ^{[4
]}

Perrett, K. P. ^{[35
,36
]}

Plested, J. S. ^{[17
]}

Richmond, P. C. ^{[37
]}

Snape, M. D. ^{[24
,25
]}

Shakib, J. H. ^{[40
]}

Shinde, V. ^{[17
]}

Stoney, T. ^{[37
]}

Thomas, D. N. ^{[17
]}

Tita, A. T. ^{[31
,32
]}

Varner, M. W. ^{[41
]}

Vatish, M. ^{[26
]}

Vrbicky, K. ^{[42
]}

Wen, J. ^{[17
]}

Zaman, K. ^{[43
]}

Zar, H. J. ^{[6
]}

机构：

[1] Univ Witwatersrand, Med Res Council, Resp & Meningeal Pathogens Res Unit, Johannesburg, South Africa

[2] Univ Witwatersrand, Vaccine Preventable Dis, Dept Sci & Technol, Natl Res Fdn, Johannesburg, South Africa

[3] Wits Reprod Hlth & HIV Inst, Shandukani Res Ctr, Johannesburg, South Africa

[4] Setshaba Res Ctr, Soshanguve, South Africa

[5] Stellenbosch Univ, Tygerberg Hosp, Family Ctr Res Ubuntu, Dept Paediat & Child Hlth, Cape Town, South Africa

[6] Univ Cape Town, South African Med Res Council, Dept Paediat & Child Hlth, Red Cross War Mem Childrens Hosp,Unit Child & Ado, Cape Town, South Africa

[7] Fdn INFANT, Buenos Aires, DF, Argentina

[8] Hosp Mil Cent Dr Cosme Argerich, Buenos Aires, DF, Argentina

[9] Natl Sci & Tech Res Council, Buenos Aires, DF, Argentina

[10] Hosp Nino Jesus, Dept Pediat Pulmonol, San Miguel De Tucuman, Argentina

[11] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA

[12] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

[13] Univ Auckland, Middlemore Hosp, Auckland, New Zealand

[14] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA

[15] Childrens Hosp Colorado, Colorado Sch Publ Hlth, Ctr Global Hlth, Aurora, CO USA

[16] Duke Univ, Dept Obstet & Gynecol, Durham, NC USA

[17] Novavax, 22 Firstfield Rd, Gaithersburg, MD 20878 USA

[18] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Int Ctr Maternal & Newborn Hlth, Baltimore, MD USA

[19] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Amer Indian Hlth, Dept Int Hlth, Baltimore, MD USA

[20] St Georges Univ London, Vaccine Inst, London, England

[21] St Georges Univ London, Vasc Biol Res Ctr, Mol & Clin Sci Res Inst, London, England

[22] Univ Southampton, Paediat Infect Dis Clin & Expt Sci, Southampton, Hants, England

[23] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England

[24] Univ Oxford, Dept Paediat, Oxford Vaccine Grp, Oxford, England

[25] Univ Oxford, Natl Inst Hlth Res, Oxford Biomed Res Ctr, Oxford, England

[26] Univ Oxford, Nuffield Dept Womens & Reprod Hlth, Oxford, England

[27] Univ Washington, Dept Pediat, Seattle Childrens Hosp, Seattle, WA 98195 USA

[28] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA

[29] Res Inst Trop Med, Muntinlupa, Philippines

[30] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA

[31] Univ Alabama Birmingham, Dept Obstet & Gynecol, Div Maternal Fetal Med, Birmingham, AL 35294 USA

[32] Univ Alabama Birmingham, Ctr Womens Reprod Hlth, Birmingham, AL USA

[33] Univ Adelaide, Womens & Childrens Hosp, Adelaide, SA, Australia

[34] Univ Adelaide, Robinson Res Inst, Adelaide, SA, Australia

[35] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Parkville, Vic, Australia

[36] Murdoch Childrens Res Inst, Parkville, Vic, Australia

[37] Univ Western Australia, Perth Childrens Hosp, Wesfarmers Ctr Vaccines & Infect Dis, Telethon Kids Inst,Div Paediat,Sch Med, Perth, WA, Australia

[38] Marshfield Clin Res Inst, Marshfield, WI USA

[39] Univ Santiago de Compostela, Pediat Clin Infectol & Traslac, Hosp Clin, Santiago De Compostela, Spain

[40] Univ Utah, Sch Med, Dept Pediat, Div Gen Pediat,Hlth Sci Ctr, Salt Lake City, UT USA

[41] Univ Utah, Dept Obstet & Gynecol, Hlth Sci Ctr, Salt Lake City, UT USA

[42] Meridian Clin Res, Norfolk, NE USA

[43] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2020年 / 383卷 / 05期

关键词：

DISEASE; BLIND;

D O I：

10.1056/NEJMoa1908380

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BackgroundRespiratory syncytial virus (RSV) is the dominant cause of severe lower respiratory tract infection in infants, with the most severe cases concentrated among younger infants. MethodsHealthy 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%). ResultsA 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. ConclusionsRSV 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. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov NCT02624947.) This randomized trial of RSV F protein nanoparticle vaccination during pregnancy did not show efficacy (according to the prespecified success criterion) against RSV-associated, medically significant lower respiratory tract infection but suggested possible benefits with respect to other RSV-related outcomes.

引用

页码：426 / 439

页数：14

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