A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA

被引：229

作者：

Ewer, K. ^{[1
,2
,3
]}

Rampling, T. ^{[1
,2
,3
]}

Venkatraman, N. ^{[1
,2
,3
]}

Bowyer, G. ^{[1
,2
,3
]}

Wright, D. ^{[1
,2
,3
]}

Lambe, T. ^{[1
,2
,3
]}

Imoukhuede, E. B. ^{[1
,2
,3
]}

Payne, R. ^{[1
,2
,3
]}

Fehling, S. K. ^{[6
]}

Strecker, T. ^{[6
]}

Biedenkopf, N. ^{[6
]}

Kraehling, V. ^{[6
]}

Tully, C. M. ^{[1
,2
,3
]}

Edwards, N. J. ^{[1
,2
,3
]}

Bentley, E. M. ^{[4
]}

Samuel, D. ^{[5
]}

Labbe, G. ^{[1
,2
,3
]}

Jin, J. ^{[1
,2
,3
]}

Gibani, M. ^{[1
,2
,3
]}

Minhinnick, A. ^{[1
,2
,3
]}

Wilkie, M. ^{[1
,2
,3
]}

Poulton, I. ^{[1
,2
,3
]}

Lella, N. ^{[1
,2
,3
]}

Roberts, R. ^{[1
,2
,3
]}

Hartnell, F. ^{[1
,2
,3
]}

Bliss, C. ^{[1
,2
,3
]}

Sierra-Davidson, K. ^{[1
,2
,3
]}

Powlson, J. ^{[1
,2
,3
]}

Berrie, E. ^{[1
,2
,3
]}

Tedder, R. ^{[5
]}

Roman, F. ^{[9
]}

De Ryck, I. ^{[9
]}

Nicosia, A. ^{[10
,11
,12
]}

Sullivan, N. J. ^{[13
]}

Stanley, D. A. ^{[13
]}

Mbaya, O. T. ^{[13
]}

Ledgerwood, J. E. ^{[13
]}

Schwartz, R. M. ^{[13
]}

Siani, L. ^{[10
]}

Colloca, S. ^{[10
]}

Folgori, A. ^{[10
]}

Di Marco, S. ^{[10
]}

Cortese, R. ^{[15
]}

Wright, E. ^{[4
]}

Becker, S. ^{[6
,7
]}

Graham, B. S. ^{[13
]}

Koup, R. A. ^{[13
]}

Levine, M. M. ^{[14
]}

Volkmann, A. ^{[8
]}

Chaplin, P. ^{[8
]}

机构：

[1] Univ Oxford, Jenner Inst, Old Rd Campus Res Bldg, Oxford OX3 7DQ, England

[2] Univ Oxford, Ctr Clin Vaccinol & Trop Med, Oxford OX3 7DQ, England

[3] Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England

[4] Univ Westminster, Fac Sci & Technol, Viral Pseudotype Unit, London W1R 8AL, England

[5] Publ Hlth Agcy, Virus Reference Dept, London, England

[6] Univ Marburg, Inst Virol, D-35032 Marburg, Germany

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

[8] Bavarian Nord, Martinsried, Germany

[9] GlaxoSmithKline Biol, Rixensart, Belgium

[10] ReiThera, Rome, Italy

[11] Univ Naples Federico II, CEINGE, Naples, Italy

[12] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy

[13] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[14] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA

[15] Keires, Basel, Switzerland

来源：

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

基金：

英国惠康基金;

关键词：

PROTECTS NONHUMAN-PRIMATES; IMMUNITY; VIRUS; CHALLENGE; INFECTION; HUMANS;

D O I：

10.1056/NEJMoa1411627

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak. METHODS In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels - 1x10(10) viral particles, 2.5x10(10) viral particles, and 5x10(10) viral particles - with 20 participants in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 participants and evaluated a reduced prime-boost interval in another 16 participants. We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) to determine relative potency and assess durability. RESULTS No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). CONCLUSIONS The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to ZEBOV that were superior to those induced by the ChAd3 vaccine alone.

引用

页码：1635 / 1646

页数：12

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