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Highly protective antimalarial antibodies via precision library generation and yeast display screening

The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis...

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Autores principales: Banach, Bailey B., Tripathi, Prabhanshu, Da Silva Pereira, Lais, Gorman, Jason, Nguyen, Thuy Duong, Dillon, Marlon, Fahad, Ahmed S., Kiyuka, Patience K., Madan, Bharat, Wolfe, Jacy R., Bonilla, Brian, Flynn, Barbara, Francica, Joseph R., Hurlburt, Nicholas K., Kisalu, Neville K., Liu, Tracy, Ou, Li, Rawi, Reda, Schön, Arne, Shen, Chen-Hsiang, Teng, I-Ting, Zhang, Baoshan, Pancera, Marie, Idris, Azza H., Seder, Robert A., Kwong, Peter D., DeKosky, Brandon J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242090/
https://www.ncbi.nlm.nih.gov/pubmed/35736810
http://dx.doi.org/10.1084/jem.20220323
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author Banach, Bailey B.
Tripathi, Prabhanshu
Da Silva Pereira, Lais
Gorman, Jason
Nguyen, Thuy Duong
Dillon, Marlon
Fahad, Ahmed S.
Kiyuka, Patience K.
Madan, Bharat
Wolfe, Jacy R.
Bonilla, Brian
Flynn, Barbara
Francica, Joseph R.
Hurlburt, Nicholas K.
Kisalu, Neville K.
Liu, Tracy
Ou, Li
Rawi, Reda
Schön, Arne
Shen, Chen-Hsiang
Teng, I-Ting
Zhang, Baoshan
Pancera, Marie
Idris, Azza H.
Seder, Robert A.
Kwong, Peter D.
DeKosky, Brandon J.
author_facet Banach, Bailey B.
Tripathi, Prabhanshu
Da Silva Pereira, Lais
Gorman, Jason
Nguyen, Thuy Duong
Dillon, Marlon
Fahad, Ahmed S.
Kiyuka, Patience K.
Madan, Bharat
Wolfe, Jacy R.
Bonilla, Brian
Flynn, Barbara
Francica, Joseph R.
Hurlburt, Nicholas K.
Kisalu, Neville K.
Liu, Tracy
Ou, Li
Rawi, Reda
Schön, Arne
Shen, Chen-Hsiang
Teng, I-Ting
Zhang, Baoshan
Pancera, Marie
Idris, Azza H.
Seder, Robert A.
Kwong, Peter D.
DeKosky, Brandon J.
author_sort Banach, Bailey B.
collection PubMed
description The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis and DNA shuffling to screen precise gene-variant yeast display libraries for improved PfCSP antigen recognition. We identified several mutations that improved recognition, predominately in framework regions, and combined these to produce a panel of antibody variants. The most improved antibody, CIS43_Var10, had three mutations and showed approximately sixfold enhanced protective potency in vivo compared to CIS43. Co-crystal and cryo-electron microscopy structures of CIS43_Var10 with the peptide epitope or with PfCSP, respectively, revealed functional roles for each of these mutations. The unbiased site-directed mutagenesis and screening pipeline described here represent a powerful approach to enhance protective potency and to enable broader clinical use of antimalarial antibodies.
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spelling pubmed-92420902023-02-01 Highly protective antimalarial antibodies via precision library generation and yeast display screening Banach, Bailey B. Tripathi, Prabhanshu Da Silva Pereira, Lais Gorman, Jason Nguyen, Thuy Duong Dillon, Marlon Fahad, Ahmed S. Kiyuka, Patience K. Madan, Bharat Wolfe, Jacy R. Bonilla, Brian Flynn, Barbara Francica, Joseph R. Hurlburt, Nicholas K. Kisalu, Neville K. Liu, Tracy Ou, Li Rawi, Reda Schön, Arne Shen, Chen-Hsiang Teng, I-Ting Zhang, Baoshan Pancera, Marie Idris, Azza H. Seder, Robert A. Kwong, Peter D. DeKosky, Brandon J. J Exp Med Technical Advances and Resources The monoclonal antibody CIS43 targets the Plasmodium falciparum circumsporozoite protein (PfCSP) and prevents malaria infection in humans for up to 9 mo following a single intravenous administration. To enhance the potency and clinical utility of CIS43, we used iterative site-saturation mutagenesis and DNA shuffling to screen precise gene-variant yeast display libraries for improved PfCSP antigen recognition. We identified several mutations that improved recognition, predominately in framework regions, and combined these to produce a panel of antibody variants. The most improved antibody, CIS43_Var10, had three mutations and showed approximately sixfold enhanced protective potency in vivo compared to CIS43. Co-crystal and cryo-electron microscopy structures of CIS43_Var10 with the peptide epitope or with PfCSP, respectively, revealed functional roles for each of these mutations. The unbiased site-directed mutagenesis and screening pipeline described here represent a powerful approach to enhance protective potency and to enable broader clinical use of antimalarial antibodies. Rockefeller University Press 2022-06-23 /pmc/articles/PMC9242090/ /pubmed/35736810 http://dx.doi.org/10.1084/jem.20220323 Text en © 2022 Banach et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Technical Advances and Resources
Banach, Bailey B.
Tripathi, Prabhanshu
Da Silva Pereira, Lais
Gorman, Jason
Nguyen, Thuy Duong
Dillon, Marlon
Fahad, Ahmed S.
Kiyuka, Patience K.
Madan, Bharat
Wolfe, Jacy R.
Bonilla, Brian
Flynn, Barbara
Francica, Joseph R.
Hurlburt, Nicholas K.
Kisalu, Neville K.
Liu, Tracy
Ou, Li
Rawi, Reda
Schön, Arne
Shen, Chen-Hsiang
Teng, I-Ting
Zhang, Baoshan
Pancera, Marie
Idris, Azza H.
Seder, Robert A.
Kwong, Peter D.
DeKosky, Brandon J.
Highly protective antimalarial antibodies via precision library generation and yeast display screening
title Highly protective antimalarial antibodies via precision library generation and yeast display screening
title_full Highly protective antimalarial antibodies via precision library generation and yeast display screening
title_fullStr Highly protective antimalarial antibodies via precision library generation and yeast display screening
title_full_unstemmed Highly protective antimalarial antibodies via precision library generation and yeast display screening
title_short Highly protective antimalarial antibodies via precision library generation and yeast display screening
title_sort highly protective antimalarial antibodies via precision library generation and yeast display screening
topic Technical Advances and Resources
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9242090/
https://www.ncbi.nlm.nih.gov/pubmed/35736810
http://dx.doi.org/10.1084/jem.20220323
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