Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans
Summary: 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 neutrali...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-04-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719303274 |
| id |
doaj-05ec511fa1b1484ababd7c9c79a01ba1 |
|---|---|
| record_format |
Article |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Pramila Rijal Sean C. Elias Samara Rosendo Machado Julie Xiao Lisa Schimanski Victoria O’Dowd Terry Baker Emily Barry Simon C. Mendelsohn Catherine J. Cherry Jing Jin Geneviève M. Labbé Francesca R. Donnellan Tommy Rampling Stuart Dowall Emma Rayner Stephen Findlay-Wilson Miles Carroll Jia Guo Xiao-Ning Xu Kuan-Ying A. Huang Ayato Takada Gillian Burgess David McMillan Andy Popplewell Daniel J. Lightwood Simon J. Draper Alain R. Townsend |
| spellingShingle |
Pramila Rijal Sean C. Elias Samara Rosendo Machado Julie Xiao Lisa Schimanski Victoria O’Dowd Terry Baker Emily Barry Simon C. Mendelsohn Catherine J. Cherry Jing Jin Geneviève M. Labbé Francesca R. Donnellan Tommy Rampling Stuart Dowall Emma Rayner Stephen Findlay-Wilson Miles Carroll Jia Guo Xiao-Ning Xu Kuan-Ying A. Huang Ayato Takada Gillian Burgess David McMillan Andy Popplewell Daniel J. Lightwood Simon J. Draper Alain R. Townsend Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans Cell Reports |
| author_facet |
Pramila Rijal Sean C. Elias Samara Rosendo Machado Julie Xiao Lisa Schimanski Victoria O’Dowd Terry Baker Emily Barry Simon C. Mendelsohn Catherine J. Cherry Jing Jin Geneviève M. Labbé Francesca R. Donnellan Tommy Rampling Stuart Dowall Emma Rayner Stephen Findlay-Wilson Miles Carroll Jia Guo Xiao-Ning Xu Kuan-Ying A. Huang Ayato Takada Gillian Burgess David McMillan Andy Popplewell Daniel J. Lightwood Simon J. Draper Alain R. Townsend |
| author_sort |
Pramila Rijal |
| title |
Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans |
| title_short |
Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans |
| title_full |
Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans |
| title_fullStr |
Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans |
| title_full_unstemmed |
Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated Humans |
| title_sort |
therapeutic monoclonal antibodies for ebola virus infection derived from vaccinated humans |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2019-04-01 |
| description |
Summary: 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. : Most antibodies used for Ebola virus treatment originate from convalescent donors or highly immunized animals. Rijal et al. find that monoclonal antibodies isolated early after vaccination from humans can be powerfully therapeutic, despite the relative immaturity of their sequences. Vaccine trials therefore can provide a valuable source of therapeutic antibodies. Keywords: Ebola virus, human monoclonal antibodies, immunotherapy, therapeutic antibodies, guinea pig model, Ebola virus glycoprotein epitopes, E-S-FLU virus, antibody binding kinetics, affinity maturation |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124719303274 |
| work_keys_str_mv |
AT pramilarijal therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT seancelias therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT samararosendomachado therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT juliexiao therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT lisaschimanski therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT victoriaodowd therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT terrybaker therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT emilybarry therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT simoncmendelsohn therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT catherinejcherry therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT jingjin therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT genevievemlabbe therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT francescardonnellan therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT tommyrampling therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT stuartdowall therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT emmarayner therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT stephenfindlaywilson therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT milescarroll therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT jiaguo therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT xiaoningxu therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT kuanyingahuang therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT ayatotakada therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT gillianburgess therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT davidmcmillan therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT andypopplewell therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT danieljlightwood therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT simonjdraper therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans AT alainrtownsend therapeuticmonoclonalantibodiesforebolavirusinfectionderivedfromvaccinatedhumans |
| _version_ |
1724920524954402816 |
| spelling |
doaj-05ec511fa1b1484ababd7c9c79a01ba12020-11-25T02:10:08ZengElsevierCell Reports2211-12472019-04-01271172186.e7Therapeutic Monoclonal Antibodies for Ebola Virus Infection Derived from Vaccinated HumansPramila Rijal0Sean C. Elias1Samara Rosendo Machado2Julie Xiao3Lisa Schimanski4Victoria O’Dowd5Terry Baker6Emily Barry7Simon C. Mendelsohn8Catherine J. Cherry9Jing Jin10Geneviève M. Labbé11Francesca R. Donnellan12Tommy Rampling13Stuart Dowall14Emma Rayner15Stephen Findlay-Wilson16Miles Carroll17Jia Guo18Xiao-Ning Xu19Kuan-Ying A. Huang20Ayato Takada21Gillian Burgess22David McMillan23Andy Popplewell24Daniel J. Lightwood25Simon J. Draper26Alain R. Townsend27MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK; Corresponding authorJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UKUCB Pharma, Slough SL1 3WE, UKUCB Pharma, Slough SL1 3WE, UKUCB Pharma, Slough SL1 3WE, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKPublic Health England, Porton Down, Wiltshire, UKPublic Health England, Porton Down, Wiltshire, UKPublic Health England, Porton Down, Wiltshire, UKPublic Health England, Porton Down, Wiltshire, UKCentre for Immunology and Vaccinology, Chelsea & Westminster Hospital, Faculty of Medicine, Imperial College, London, UKCentre for Immunology and Vaccinology, Chelsea & Westminster Hospital, Faculty of Medicine, Imperial College, London, UKDivision of Paediatric Infectious Diseases, Department of Paediatrics, Chang Gung Memorial Hospital, Taoyuan, TaiwanDivision of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, JapanUCB Pharma, Slough SL1 3WE, UKUCB Pharma, Slough SL1 3WE, UKUCB Pharma, Slough SL1 3WE, UKUCB Pharma, Slough SL1 3WE, UKJenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UKMRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK; Corresponding authorSummary: 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. : Most antibodies used for Ebola virus treatment originate from convalescent donors or highly immunized animals. Rijal et al. find that monoclonal antibodies isolated early after vaccination from humans can be powerfully therapeutic, despite the relative immaturity of their sequences. Vaccine trials therefore can provide a valuable source of therapeutic antibodies. Keywords: Ebola virus, human monoclonal antibodies, immunotherapy, therapeutic antibodies, guinea pig model, Ebola virus glycoprotein epitopes, E-S-FLU virus, antibody binding kinetics, affinity maturationhttp://www.sciencedirect.com/science/article/pii/S2211124719303274 |