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dc.creatorHuang, Kuan-Ying A.
dc.creatorZhou, Daming
dc.creatorKit Tan, Tiong
dc.creatorChen, Charles
dc.creatorDuyvesteyn, Helen M. E.
dc.creatorZhao, Yuguang
dc.creatorGinn, Helen M.
dc.creatorQin, Ling
dc.creatorRijal, Pramila
dc.creatorSchimanski, Lisa
dc.creatorDonat, Robert
dc.creatorHarding, Adam
dc.creatorGilbert-Jaramillo, Javier
dc.creatorJames, William
dc.creatorTree, Julia A.
dc.creatorButtigieg, Karen
dc.creatorCarroll, Miles
dc.creatorCharlton, Sue
dc.creatorLien, Chia-En
dc.creatorLin, Meei-Yun
dc.creatorChen, Cheng-Pin
dc.creatorCheng, Shu-Hsing
dc.creatorChen, Xiaorui
dc.creatorLin, Tzou-Yien
dc.creatorFry, Elizabeth, E.
dc.creatorRen, Jingshan
dc.creatorMa, Che
dc.creatorTownsend, Alain R.
dc.creatorStuart, David I.
dc.date.accessioned2022-04-22T20:27:51Z
dc.date.available2022-04-22T20:27:51Z
dc.date.issued2022-01-01
dc.identifier.citationHuang KYA, Zhou D, Tan TK, Chen C, Duyvesteyn HME, Zhao Y, Ginn HM, Qin L, Rijal P, Schimanski L, Donat R, Harding A, Gilbert-Jaramillo J, James W, Tree JA, Buttigieg K, Carroll M, Charlton S, Lien CE, Lin MY, Chen CP, Cheng SH, Chen X, Lin TY, Fry EE, Ren J, Ma C, Townsend AR, Stuart DI. Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2. Theranostics 2022; 12(1):1-17. doi:10.7150/thno.65563. Available from https://www.thno.org/v12p0001.htm
dc.identifier.issn1838-7640
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/7552
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7574
dc.description.abstractBackground: Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Methods: Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their neutralization efficacy in vitro. Here, we elucidate the mechanism of action of antibodies and dissect antibodies at the epitope level, which leads to a formation of a potent antibody cocktail. Results: We found that representative antibodies which target non-overlapping epitopes are effective against wild type virus and recently emerging variants of concern, whilst being encoded by antibody genes with few somatic mutations. Neutralization is associated with the inhibition of binding of viral RBD to ACE2 and possibly of the subsequent fusion process. Structural analysis of representative antibodies, by cryo-electron microscopy and crystallography, reveals that they have some unique aspects that are of potential value while sharing some features in common with previously reported neutralizing monoclonal antibodies. For instance, one has a common VH 3-53 public variable region yet is unusually resilient to mutation at residue 501 of the RBD. We evaluate the in vivo efficacy of an antibody cocktail consisting of two potent non-competing anti-RBD antibodies in a Syrian hamster model. We demonstrate that the cocktail prevents weight loss, reduces lung viral load and attenuates pulmonary inflammation in hamsters in both prophylactic and therapeutic settings. Although neutralization of one of these antibodies is abrogated by the mutations of variant B.1.351, it is also possible to produce a bi-valent cocktail of antibodies both of which are resilient to variants B.1.1.7, B.1.351 and B.1.617.2. Conclusions: These findings support the up-to-date and rational design of an anti-RBD antibody cocktail as a therapeutic candidate against COVID-19.
dc.format.extent17 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofCOVID-19 Research
dc.relation.haspartTheranostics, Vol. 12, No. 1
dc.relation.isreferencedbyIvyspring
dc.rightsAttribution CC BY
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSARS-CoV-2
dc.subjectHuman monoclonal antibody
dc.subjectIn vitro and in vivo function
dc.subjectAntibody-antigen complex
dc.subjectReceptor-binding domain epitope
dc.subjectAntibody cocktail
dc.titleStructures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2
dc.typeText
dc.type.genreJournal article
dc.description.departmentBiology
dc.relation.doihttps://doi.org/10.7150/thno.65563
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.temple.creatorChen, Charles
refterms.dateFOA2022-04-22T20:27:51Z


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