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A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant

Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of c...

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Autores principales: Hingankar, Nitin, Deshpande, Suprit, Das, Payel, Rizvi, Zaigham Abbas, Wibmer, Constantinos Kurt, Mashilo, Poppy, Ansari, Mohammed Yousuf, Burns, Alison, Barman, Shawn, Zhao, Fangzhu, Mukherjee, Sohini, Torres, Jonathan L., Chattopadhyay, Souvick, Mehdi, Farha, Sutar, Jyoti, Rathore, Deepak Kumar, Pargai, Kamal, Singh, Janmejay, Sonar, Sudipta, Jakhar, Kamini, Dandotiya, Jyotsna, Bhattacharyya, Sankar, Mani, Shailendra, Samal, Sweety, Singh, Savita, Kshetrapal, Pallavi, Thiruvengadam, Ramachandran, Batra, Gaurav, Medigeshi, Guruprasad, Ward, Andrew B., Bhatnagar, Shinjini, Awasthi, Amit, Sok, Devin, Bhattacharya, Jayanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089897/
https://www.ncbi.nlm.nih.gov/pubmed/35482816
http://dx.doi.org/10.1371/journal.ppat.1010465
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author Hingankar, Nitin
Deshpande, Suprit
Das, Payel
Rizvi, Zaigham Abbas
Wibmer, Constantinos Kurt
Mashilo, Poppy
Ansari, Mohammed Yousuf
Burns, Alison
Barman, Shawn
Zhao, Fangzhu
Mukherjee, Sohini
Torres, Jonathan L.
Chattopadhyay, Souvick
Mehdi, Farha
Sutar, Jyoti
Rathore, Deepak Kumar
Pargai, Kamal
Singh, Janmejay
Sonar, Sudipta
Jakhar, Kamini
Dandotiya, Jyotsna
Bhattacharyya, Sankar
Mani, Shailendra
Samal, Sweety
Singh, Savita
Kshetrapal, Pallavi
Thiruvengadam, Ramachandran
Batra, Gaurav
Medigeshi, Guruprasad
Ward, Andrew B.
Bhatnagar, Shinjini
Awasthi, Amit
Sok, Devin
Bhattacharya, Jayanta
author_facet Hingankar, Nitin
Deshpande, Suprit
Das, Payel
Rizvi, Zaigham Abbas
Wibmer, Constantinos Kurt
Mashilo, Poppy
Ansari, Mohammed Yousuf
Burns, Alison
Barman, Shawn
Zhao, Fangzhu
Mukherjee, Sohini
Torres, Jonathan L.
Chattopadhyay, Souvick
Mehdi, Farha
Sutar, Jyoti
Rathore, Deepak Kumar
Pargai, Kamal
Singh, Janmejay
Sonar, Sudipta
Jakhar, Kamini
Dandotiya, Jyotsna
Bhattacharyya, Sankar
Mani, Shailendra
Samal, Sweety
Singh, Savita
Kshetrapal, Pallavi
Thiruvengadam, Ramachandran
Batra, Gaurav
Medigeshi, Guruprasad
Ward, Andrew B.
Bhatnagar, Shinjini
Awasthi, Amit
Sok, Devin
Bhattacharya, Jayanta
author_sort Hingankar, Nitin
collection PubMed
description Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness.
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spelling pubmed-90898972022-05-11 A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant Hingankar, Nitin Deshpande, Suprit Das, Payel Rizvi, Zaigham Abbas Wibmer, Constantinos Kurt Mashilo, Poppy Ansari, Mohammed Yousuf Burns, Alison Barman, Shawn Zhao, Fangzhu Mukherjee, Sohini Torres, Jonathan L. Chattopadhyay, Souvick Mehdi, Farha Sutar, Jyoti Rathore, Deepak Kumar Pargai, Kamal Singh, Janmejay Sonar, Sudipta Jakhar, Kamini Dandotiya, Jyotsna Bhattacharyya, Sankar Mani, Shailendra Samal, Sweety Singh, Savita Kshetrapal, Pallavi Thiruvengadam, Ramachandran Batra, Gaurav Medigeshi, Guruprasad Ward, Andrew B. Bhatnagar, Shinjini Awasthi, Amit Sok, Devin Bhattacharya, Jayanta PLoS Pathog Research Article Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness. Public Library of Science 2022-04-28 /pmc/articles/PMC9089897/ /pubmed/35482816 http://dx.doi.org/10.1371/journal.ppat.1010465 Text en © 2022 Hingankar et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hingankar, Nitin
Deshpande, Suprit
Das, Payel
Rizvi, Zaigham Abbas
Wibmer, Constantinos Kurt
Mashilo, Poppy
Ansari, Mohammed Yousuf
Burns, Alison
Barman, Shawn
Zhao, Fangzhu
Mukherjee, Sohini
Torres, Jonathan L.
Chattopadhyay, Souvick
Mehdi, Farha
Sutar, Jyoti
Rathore, Deepak Kumar
Pargai, Kamal
Singh, Janmejay
Sonar, Sudipta
Jakhar, Kamini
Dandotiya, Jyotsna
Bhattacharyya, Sankar
Mani, Shailendra
Samal, Sweety
Singh, Savita
Kshetrapal, Pallavi
Thiruvengadam, Ramachandran
Batra, Gaurav
Medigeshi, Guruprasad
Ward, Andrew B.
Bhatnagar, Shinjini
Awasthi, Amit
Sok, Devin
Bhattacharya, Jayanta
A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
title A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
title_full A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
title_fullStr A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
title_full_unstemmed A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
title_short A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant
title_sort combination of potently neutralizing monoclonal antibodies isolated from an indian convalescent donor protects against the sars-cov-2 delta variant
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9089897/
https://www.ncbi.nlm.nih.gov/pubmed/35482816
http://dx.doi.org/10.1371/journal.ppat.1010465
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