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

Autor: Nitin Hingankar, Suprit Deshpande, Payel Das, Zaigham Abbas Rizvi, Constantinos Kurt Wibmer, Poppy Mashilo, Mohammed Yousuf Ansari, Alison Burns, Shawn Barman, Fangzhu Zhao, Sohini Mukherjee, Jonathan L Torres, Souvick Chattopadhyay, Farha Mehdi, Jyoti Sutar, Deepak Kumar Rathore, Kamal Pargai, Janmejay Singh, Sudipta Sonar, Kamini Jakhar, Jyotsna Dandotiya, Sankar Bhattacharyya, Shailendra Mani, Sweety Samal, Savita Singh, Pallavi Kshetrapal, Ramachandran Thiruvengadam, Gaurav Batra, Guruprasad Medigeshi, Andrew B Ward, Shinjini Bhatnagar, Amit Awasthi, Devin Sok, Jayanta Bhattacharya
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: PLoS Pathogens, Vol 18, Iss 4, p e1010465 (2022)
Druh dokumentu: article
ISSN: 1553-7366
1553-7374
DOI: 10.1371/journal.ppat.1010465
Popis: 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.
Databáze: Directory of Open Access Journals
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