Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe

被引：297

作者：

Agnandji, S. T. ^{[2
,3
,4
]}

Huttner, A. ^{[14
,15
]}

Zinser, M. E. ^{[5
]}

Njuguna, P. ^{[24
]}

Dahlke, C. ^{[5
,7
]}

Fernandes, J. F. ^{[2
,3
,4
]}

Yerly, S. ^{[20
,21
]}

Dayer, J. -A. ^{[15
]}

Kraehling, V. ^{[11
,12
]}

Kasonta, R. ^{[5
,13
]}

Adegnika, A. A. ^{[2
,3
,4
,25
]}

Altfeld, M. ^{[8
]}

Auderset, F. ^{[22
]}

Bache, E. B. ^{[2
,3
,4
]}

Biedenkopf, N. ^{[11
,12
]}

Borregaard, S. ^{[9
]}

Brosnahan, J. S. ^{[2
,3
,4
]}

Burrow, R. ^{[27
]}

Combescure, C. ^{[16
]}

Desmeules, J. ^{[19
]}

Eickmann, M. ^{[11
,12
]}

Fehling, S. K. ^{[11
,12
]}

Finckh, A. ^{[17
]}

Goncalves, A. R. ^{[20
,21
]}

Grobusch, M. P. ^{[2
,3
,4
,26
]}

Hooper, J. ^{[28
,29
]}

Jambrecina, A. ^{[9
]}

Kabwende, A. L. ^{[2
,3
,4
]}

Kaya, G. ^{[18
]}

Kimani, D. ^{[24
]}

Lell, B. ^{[2
,3
,4
]}

Lemaitre, B. ^{[22
]}

Lohse, A. W. ^{[5
]}

Massinga-Loembe, M. ^{[2
,3
,4
]}

Matthey, A. ^{[19
]}

Mordmueller, B. ^{[2
,3
,4
]}

Nolting, A. ^{[5
,7
]}

Ogwang, C. ^{[24
]}

Ramharter, M. ^{[2
,3
,4
,30
]}

Schmidt-Chanasit, J. ^{[7
,10
]}

Schmiedel, S. ^{[5
]}

Silvera, P. ^{[28
,29
]}

Stahl, F. R. ^{[6
]}

Staines, H. M. ^{[27
]}

Strecker, T. ^{[11
,12
]}

Stubbe, H. C. ^{[5
,7
]}

Tsofa, B. ^{[24
]}

Zaki, S. ^{[31
]}

Fast, P. ^{[23
,32
]}

Moorthy, V. ^{[23
]}

机构：

[1] Univ Hosp Geneva, Ctr Vaccinol, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland

[2] Ctr Rech Med Lambarene, Lambarene, Gabon

[3] Univ Klinikum Tubinen, Inst Tropenmed, Tubingen, Germany

[4] German Ctr Infect Res, Tubingen, Germany

[5] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany

[6] Inst Clin Chem & Lab Med, Hamburg, Germany

[7] German Ctr Infect Res, Partner Site Standort Hamburg lUBECK Borstel, Hamburg, Germany

[8] Leibniz Inst Expt Virol, Heinrich Pette Inst, Hamburg, Germany

[9] Clin Trial Ctr North, Hamburg, Germany

[10] WHO, Collaborating Ctr Arbovirus & Hemorrhag Fever Ref, Natl Reference Ctr Trop Infect Dis, Bernhard Nocht Inst Trop Med, Hamburg, Germany

[11] Univ Marburg, Inst Virol, Partner Site Giessen Marburg Langen, D-35032 Marburg, Germany

[12] German Ctr Infect Res DZIF, Partner Site Giessen Marburg Langen, Marburg, Germany

[13] Paul Ehrlich Inst, Div Vet Med, Langen, Germany

[14] Univ Hosp Geneva, Infect Control Program, CH-1211 Geneva 4, Switzerland

[15] Univ Hosp Geneva, Div Infect Dis, CH-1211 Geneva 4, Switzerland

[16] Univ Hosp Geneva, Div Clin Epidemiol, CH-1211 Geneva 4, Switzerland

[17] Univ Hosp Geneva, Div Rheumatol, CH-1211 Geneva 4, Switzerland

[18] Univ Hosp Geneva, Div Dermatol, CH-1211 Geneva 4, Switzerland

[19] Univ Hosp Geneva, Clin Res Ctr, CH-1211 Geneva 4, Switzerland

[20] Univ Hosp Geneva, Fac Med, CH-1211 Geneva 4, Switzerland

[21] Univ Hosp Geneva, Virol Lab, CH-1211 Geneva 4, Switzerland

[22] WHO, Collaborat Ctr Vaccinol, Fac Med, Geneva, Switzerland

[23] WHO, Geneva, Switzerland

[24] Ctr Geog Med Res, Kenya Med Res Inst, Wellcome Trust Res Program, Kilifi, Kenya

[25] Leiden Univ, Dept Parasitol, Med Ctr, Leiden, Netherlands

[26] Univ Amsterdam, Acad Med Ctr, Ctr Trop Med & Travel Med, Dept Infect Dis,Div Internal Med, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands

[27] Univ London, Inst Infect & Immun, London WC1E 7HU, England

[28] US Army, Dept Mol Virol, Med Res Inst Infect, Frederick, MD USA

[29] US Army, Div Translat Sci, Med Res Inst Infect, Frederick, MD USA

[30] Med Univ Vienna, Dept Med 1, Div Infect Dis & Trop Med, Vienna, Austria

[31] Ctr Dis Control & Prevent, Infect Dis Pathol Branch, Atlanta, GA USA

[32] Int AIDS Vaccine Initiat, New York, NY USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2016年 / 374卷 / 17期

基金：

英国惠康基金;

关键词：

VESICULAR STOMATITIS-VIRUS; PROTECTS NONHUMAN-PRIMATES; MARBURG VIRUS; INFECTION; IMMUNITY;

D O I：

10.1056/NEJMoa1502924

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glyco-protein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy.

引用

页码：1647 / 1660

页数：14

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