Randomized Trial of Vaccines for Zaire Ebola Virus Disease

被引：45

作者：

Kieh, Mark ^{[1
]}

Richert, Laura ^{[2
,3
,4
]}

Beavogui, Abdoul H. ^{[9
]}

Grund, Birgit ^{[11
]}

Leigh, Bailah ^{[12
]}

D'Ortenzio, Eric ^{[5
,6
,7
]}

Doumbia, Seydou ^{[13
]}

Lhomme, Edouard ^{[2
,3
,4
]}

Sow, Samba ^{[15
]}

Vatrinet, Renaud ^{[5
]}

Roy, Celine ^{[3
,4
]}

Kennedy, Stephen B. ^{[1
]}

Faye, Sylvain ^{[17
]}

Lees, Shelley ^{[19
]}

Millimouno, Niouma P. ^{[18
]}

Camara, Alseny M. ^{[18
]}

Samai, Mohamed ^{[12
]}

Deen, Gibrilla F. ^{[12
]}

Doumbia, Moussa ^{[14
]}

Esperou, Helene ^{[5
]}

Pierson, Jerome ^{[16
]}

Watson-Jones, Deborah ^{[19
]}

Diallo, Alpha ^{[5
,6
]}

Wentworth, Deborah ^{[10
]}

McLean, Chelsea ^{[20
]}

Simon, Jakub ^{[21
]}

Wiedemann, Aurelie ^{[5
,8
]}

Dighero-Kemp, Bonnie ^{[16
]}

Hensley, Lisa ^{[16
]}

Lane, H. Clifford ^{[16
]}

Levy, Yves ^{[5
,8
]}

Piot, Peter ^{[19
]}

Greenwood, Brian ^{[19
]}

Chene, Genevieve ^{[3
,4
]}

Neaton, James ^{[10
]}

Yazdanpanah, Yazdan ^{[5
,6
,7
]}

机构：

[1] Partnership Res Ebola Virus Liberia, Monrovia, CA USA

[2] Bordeaux Populat Hlth, Unin 1219, INRIA, Stat Syst Biol & Translat Med, Bordeaux, France

[3] Euclid French Clin Res Infrastruct Network Clin T, Bordeaux, France

[4] Univ Bordeaux, INSERM, Inst Bergonie, Ctr Hosp Univ Bordeaux,Clin Invest Ctr,Clin Epide, Bordeaux, France

[5] INSERM, Paris, France

[6] ANRS Emerging Infect Dis, France Rech Nord & Sud Sida HIV Hepatites, Paris, France

[7] Hop Bichat Claude Bernard, AP HP, Serv Malad Infect & Trop, Paris, France

[8] Univ Paris Est Creteil, Henri Mondor Hosp, Vaccine Res Inst, Creteil, France

[9] Ctr Natl Format & Rech Sante Rurale Maferinyah, Maferinyah, Guinea

[10] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA

[11] Univ Minnesota, Sch Stat, Minneapolis, MN USA

[12] Univ Sierra Leone, Coll Med & Allied Hlth Sci, Freetown, Sierra Leone

[13] Univ Sci Tech & Technol Bamako, Univ Clin Res Ctr, Bamako, Mali

[14] Minist Sante, Ctr Dev Vaccins, Bamako, Mali

[15] Univ Maryland, Ctr Vaccine Dev & Global Hlth, Baltimore, MD 21201 USA

[16] NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA

[17] Univ Cheikh Anta Diop, Fac Lettres & Sci Humaines, Dept Sociol, Dakar, Senegal

[18] Alliance Int Med Act, Dakar, Senegal

[19] London Sch Hyg & Trop Med, London, England

[20] Janssen Vaccines & Prevent, Leiden, Netherlands

[21] Merck Sharp & Dohme Ltd, Kenilworth, NJ USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2022年 / 387卷 / 26期

基金：

美国国家卫生研究院;

关键词：

RING VACCINATION; DOUBLE-BLIND; OPEN-LABEL; SAFETY; ZEBOV; IMMUNOGENICITY; GUINEA; ADULTS;

D O I：

10.1056/NEJMoa2200072

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSV Delta G-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSV Delta G-ZEBOV- GP followed by rVSV Delta G-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others

引用

页码：2411 / 2424

页数：14

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