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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

DOI: 10.1371/journal.ppat.1010465 DOI Help

Authors: Nitin Hingankar (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Suprit Deshpande (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Payel Das (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Zaigham Abbas Rizvi (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Constantinos Kurt Wibmer (National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS)) , Poppy Mashilo (National Institute for Communicable Diseases (NICD) of the National Health Laboratory Service (NHLS)) , Mohammed Yousuf Ansari (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Alison Burns (The Scripps Research Institute) , Shawn Barman (The Scripps Research Institute) , Fangzhu Zhao (The Scripps Research Institute) , Sohini Mukherjee (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Jonathan L. Torres (The Scripps Research Institute) , Souvick Chattopadhyay (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Farha Mehdi (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Jyoti Sutar (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Deepak Kumar Rathore (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Kamal Pargai (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Janmejay Singh (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Sudipta Sonar (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Kamini Jakhar (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Jyotsna Dandotiya (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Sankar Bhattacharyya (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Shailendra Mani (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Sweety Samal (Translational Health Science & Technology Institute, NCR Biotech Science Cluster,) , Savita Singh (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Pallavi Kshetrapal (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Ramachandran Thiruvengadam (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Gaurav Batra (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Guruprasad Medigeshi (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Andrew B. Ward (The Scripps Research Institute) , Shinjini Bhatnagar (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Amit Awasthi (Translational Health Science & Technology Institute, NCR Biotech Science Cluster) , Devin Sok (The Scripps Research Institute) , Jayanta Bhattacharya (ranslational Health Science & Technology Institute, NCR Biotech Science Cluster)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Plos Pathogens , VOL 18

State: Published (Approved)
Published: April 2022
Diamond Proposal Number(s): 28402

Open Access Open Access

Abstract: 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.

Journal Keywords: SARS CoV 2; Enzyme-linked immunoassays; Antibodies; Monoclonal antibodies; Mouse models; COVID 19; Body weight; Cell staining

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials, Medicine


Instruments: I04-Macromolecular Crystallography

Added On: 05/05/2022 10:01

Documents:
pnas.2117310119.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)