Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans

被引：52

作者：

Rijal, Pramila ^{[1
]}

Elias, Sean C. ^{[2
]}

Machado, Samara Rosendo ^{[1
]}

Xiao, Julie ^{[1
]}

Schimanski, Lisa ^{[1
]}

O'Dowd, Victoria ^{[3
]}

Baker, Terry ^{[3
]}

Barry, Emily ^{[3
]}

Mendelsohn, Simon C. ^{[2
]}

Cherry, Catherine J. ^{[2
]}

Jin, Jing ^{[2
]}

Labbe, Genevieve M. ^{[2
]}

Donnellan, Francesca R. ^{[2
]}

Rampling, Tommy ^{[2
]}

Dowall, Stuart ^{[4
]}

Rayner, Emma ^{[4
]}

Findlay-Wilson, Stephen ^{[4
]}

Carroll, Miles ^{[4
]}

Guo, Jia ^{[5
]}

Xu, Xiao-Ning ^{[5
]}

Huang, Kuan-Ying A. ^{[6
]}

Takada, Ayato ^{[7
]}

Burgess, Gillian ^{[3
]}

McMillan, David ^{[3
]}

Popplewell, Andy ^{[3
]}

Lightwood, Daniel J. ^{[3
]}

Draper, Simon J. ^{[2
]}

Townsend, Alain R. ^{[1
]}

机构：

[1] Univ Oxford, MRC Weatherall Inst Mol Med, Radcliffe Dept Med, MRC Human Immunol Unit, Oxford OX3 9DS, England

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

[3] UCB Pharma, Slough SL1 3WE, Berks, England

[4] Publ Hlth England, Porton Down, Wilts, England

[5] Chelsea & Westminster Hosp, Imperial Coll, Fac Med, Ctr Immunol & Vaccinol, London, England

[6] Chang Gung Mem Hosp, Dept Paediat, Div Paediat Infect Dis, Taoyuan, Taiwan

[7] Hokkaido Univ, Res Ctr Zoonosis Control, Div Global Epidemiol, Sapporo, Hokkaido, Japan

来源：

CELL REPORTS | 2019年 / 27卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

NEUTRALIZING ANTIBODIES; MEDIATED NEUTRALIZATION; AFFINITY MATURATION; NONHUMAN-PRIMATES; PROTECTION; CELLS; RESPONSES; VULNERABILITY; GLYCOPROTEIN; GENERATION;

D O I：

10.1016/j.celrep.2019.03.020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We describe therapeutic monoclonal antibodies isolated from human volunteers vaccinated with recombinant adenovirus expressing Ebola virus glycoprotein (EBOV GP) and boosted with modified vaccinia virus Ankara. Among 82 antibodies isolated from peripheral blood B cells, almost half neutralized GP pseudotyped influenza virus. The antibody response was diverse in gene usage and epitope recognition. Although close to germline in sequence, neutralizing antibodies with binding affinities in the nano-to pico-molar range, similar to "affinity matured" antibodies from convalescent donors, were found. They recognized the mucin-like domain, glycan cap, receptor binding region, and the base of the glycoprotein. A cross-reactive cocktail of four antibodies, targeting the latter three non-overlapping epitopes, given on day 3 of EBOV infection, completely protected guinea pigs. This study highlights the value of experimental vaccine trials as a rich source of therapeutic human monoclonal antibodies.

引用

页码：172 / +

页数：22

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