부산대학교 도서관

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. Author summary: SARS-CoV-2, a highly infectious and pathogenic virus that caused the COVID-19 pandemic, has led to unprecedented devastation and disruption in human health, public safety, and the global economy. The virus genome sequence has aided in the rapid development of vaccines as well as the discovery of potential therapeutic agents such as monoclonal antibodies (mAbs). In India, the emergence of the Delta variant led to a significant rise in caseloads and deaths that overwhelmed global health systems. Here, we describe the isolation of novel cross SARS-CoV-2 variant neutralizing monoclonal antibodies (mAbs) from a single Indian convalescent individual, two of which (THSC20.HVTR04 and THSC20.HVTR26) demonstrated very potent neutralization of SARS-CoV-2 variants of concern (VOC) by targeting non-overlapping epitopes in the spike protein's receptor binding domain (RBD). One of these two mAbs, THSC20.HVTR26 was also found to retain activity against the Omicron variant albeit with reduced potency. Furthermore, in a hACE2 transgenic mouse model, passive transfer of their combination conferred significant protection against infection by Delta variant at a low dose, implying that these two highly potent mAbs have the potential to be developed as products for therapeutic and preventive application against SARS-CoV-2 infection. The lessons learned from the COVID-19 pandemic emphasize the importance of a timely response through the discovery of effective mAbs as part of pandemic preparedness for future emerging infectious diseases. [ABSTRACT FROM AUTHOR]