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Updated: Sep 21, 2025
Laboratory Scale Production and Purification of a Therapeutic Antibody
Published on: January 24, 2017
Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics
Robert V House1, Thomas A Broge2, Todd J Suscovich2
1Ology Bioservices, Frederick, MD, United States of America.
Abstract:
The current global COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in a public health crisis with more than 168 million cases reported globally and more than 4.5 million deaths at the time of writing. In addition to the direct impact of the disease, the economic impact has been significant as public health measures to contain or reduce the spread have led to country wide lockdowns resulting in near closure of many sectors of the economy. Antibodies are a principal determinant of the humoral immune response to COVID-19 infections and may have the potential to reduce disease and spread of the virus. The development of monoclonal antibodies (mAbs) represents a therapeutic option that can be produced at large quantity and high quality. In the present study, a mAb combination mixture therapy was investigated for its capability to specifically neutralize SARS-CoV-2. We demonstrate that each of the antibodies bind the spike protein and neutralize the virus, preventing it from infecting cells in an in vitro cell-based assay, including multiple viral variants that are currently circulating in the human population. In addition, we investigated the effects of two different mutations in the Fc portion (YTE and LALA) of the antibody on Fc effector function and the ability to alleviate potential antibody-dependent enhancement of disease. These data demonstrate the potential of a combination of two mAbs that target two different epitopes on the SARS-CoV2 spike protein to provide protection against SARS-CoV-2 infection in humans while extending serum half-life and preventing antibody-dependent enhancement of disease.
Insights
This study shows a combination therapy of two monoclonal antibodies (mAbs) effectively neutralizes SARS-CoV-2, including variants. This approach offers potential protection against COVID-19 by enhancing antibody function and longevity.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- The COVID-19 pandemic, caused by SARS-CoV-2, presents a significant global health and economic challenge.
- Monoclonal antibodies (mAbs) are a promising therapeutic strategy for neutralizing SARS-CoV-2 and mitigating disease spread.
- Understanding antibody interactions with viral variants and Fc effector functions is crucial for developing effective treatments.
Purpose of the Study:
- To investigate a combination therapy of two monoclonal antibodies (mAbs) for neutralizing SARS-CoV-2.
- To assess the efficacy of mAbs against circulating SARS-CoV-2 variants.
- To evaluate the impact of Fc portion mutations (YTE and LALA) on antibody function and potential for antibody-dependent enhancement of disease.
Main Methods:
- In vitro cell-based assays were used to evaluate viral neutralization by mAbs.
- Binding affinity to the SARS-CoV-2 spike protein was assessed.
- Fc effector functions and antibody-dependent enhancement were studied using specific antibody mutations.
Main Results:
- Both individual mAbs demonstrated binding to the spike protein and neutralized SARS-CoV-2 in vitro.
- The mAb combination effectively neutralized multiple circulating SARS-CoV-2 variants.
- Fc mutations influenced effector functions and showed potential to prevent antibody-dependent enhancement of disease.
Conclusions:
- A combination of two mAbs targeting distinct epitopes on the SARS-CoV-2 spike protein shows potential for protecting humans against infection.
- This therapeutic strategy may extend serum half-life and prevent antibody-dependent enhancement of disease.
- Further development of mAb combination therapies holds promise for managing COVID-19.
