{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T11:38:28Z","timestamp":1780486708368,"version":"3.54.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2023,1,1]],"date-time":"2023-01-01T00:00:00Z","timestamp":1672531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["1R01AI161152-01A1"],"award-info":[{"award-number":["1R01AI161152-01A1"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020366","name":"Massachusetts Consortium on Pathogen Readiness","doi-asserted-by":"crossref","award":["280870.5116709.0016"],"award-info":[{"award-number":["280870.5116709.0016"]}],"id":[{"id":"10.13039\/100020366","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Monoclonal antibody (mAb) therapies have rapidly become a powerful class of therapeutics with applications covering a diverse range of clinical indications. Though most widely used for the treatment of cancer, mAbs are also playing an increasing role in the defense of viral infections, most recently with palivizumab for prevention and treatment of severe RSV infections in neonatal and pediatric populations. In addition, during the COVID-19 pandemic, mAbs provided a bridge to the rollout of vaccines; however, their continued role as a therapeutic option for those at greatest risk of severe disease has become limited due to the emergence of neutralization resistant Omicron variants. Although there are many techniques for the identification of mAbs, including single B cell cloning and immunization of genetically engineered mice, the low cost, rapid throughput and technological simplicity of antibody phage display has led to its widespread adoption in mAb discovery efforts. Here we used our 27-billion-member na\u00efve single-chain antibody (scFv) phage library to identify a panel of neutralizing anti-SARS-CoV-2 scFvs targeting diverse epitopes on the receptor binding domain (RBD). Although typically a routine process, we found that upon conversion to IgG, a number of our most potent clones failed to maintain their neutralization potency. Kinetic measurements confirmed similar affinity to the RBD; however, mechanistic studies provide evidence that the loss of neutralization is a result of structural limitations likely arising from initial choice of panning antigen. Thus this work highlights a risk of scFv-phage panning to mAb conversion and the importance of initial antigen selection.<\/jats:p>","DOI":"10.1093\/protein\/gzad008","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T15:27:42Z","timestamp":1691681262000},"source":"Crossref","is-referenced-by-count":2,"title":["The variable conversion of neutralizing anti-SARS-CoV-2 single-chain antibodies to IgG provides insight into RBD epitope accessibility"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-997X","authenticated-orcid":false,"given":"Matthew R","family":"Chang","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhong","family":"Ke","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"},{"name":"Harvard Medical School Department of Medicine, , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Losada Migu\u00e9ns","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Coherd","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrina","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maliwan","family":"Kamkaew","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Johnson","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Department of Virology, Immunology, and Microbiology and National Emerging Infectious Diseases Laboratories, , Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Storm","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Department of Virology, Immunology, and Microbiology and National Emerging Infectious Diseases Laboratories, , Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Honko","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Department of Virology, Immunology, and Microbiology and National Emerging Infectious Diseases Laboratories, , Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"},{"name":"Harvard Medical School Department of Medicine, , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Boston University School of Medicine Department of Virology, Immunology, and Microbiology and National Emerging Infectious Diseases Laboratories, , Boston, MA 02118, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne A","family":"Marasco","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute Department of Cancer Immunology & Virology, , Boston, MA 02215, USA"},{"name":"Harvard Medical School Department of Medicine, , Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,17]]},"reference":[{"key":"2023110705040241200_ref1","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2020.01986","volume":"11","author":"Alfaleh","year":"2020","journal-title":"Front. 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Commun."}],"container-title":["Protein Engineering, Design and Selection"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/peds\/advance-article-pdf\/doi\/10.1093\/protein\/gzad008\/51089329\/gzad008.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/peds\/article-pdf\/doi\/10.1093\/protein\/gzad008\/52760700\/gzad008.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/peds\/article-pdf\/doi\/10.1093\/protein\/gzad008\/52760700\/gzad008.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T05:04:45Z","timestamp":1699333485000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/peds\/article\/doi\/10.1093\/protein\/gzad008\/7240570"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023]]},"references-count":34,"URL":"https:\/\/doi.org\/10.1093\/protein\/gzad008","relation":{},"ISSN":["1741-0126","1741-0134"],"issn-type":[{"value":"1741-0126","type":"print"},{"value":"1741-0134","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023]]},"published":{"date-parts":[[2023]]},"article-number":"gzad008"}}