Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics
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 disea...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165815/?tool=EBI |
| _version_ | 1811248297504931840 |
|---|---|
| author | Robert V. House Thomas A. Broge Todd J. Suscovich Doris M. Snow Milan T. Tomic Genevieve Nonet Kamaljit Bajwa Guangyu Zhu Zachary Martinez Kyal Hackett Christopher G. Earnhart Nicole M. Dorsey Svetlana A. Hopkins Dalia S. Natour Heather D. Davis Michael S. Anderson Melicia R. Gainey Ronald R. Cobb |
| author_facet | Robert V. House Thomas A. Broge Todd J. Suscovich Doris M. Snow Milan T. Tomic Genevieve Nonet Kamaljit Bajwa Guangyu Zhu Zachary Martinez Kyal Hackett Christopher G. Earnhart Nicole M. Dorsey Svetlana A. Hopkins Dalia S. Natour Heather D. Davis Michael S. Anderson Melicia R. Gainey Ronald R. Cobb |
| author_sort | Robert V. House |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T15:25:35Z |
| format | Article |
| id | doaj.art-1256ef3efe654aee890a88f093d4a810 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T15:25:35Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1256ef3efe654aee890a88f093d4a8102022-12-22T03:27:16ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-01176Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeuticsRobert V. HouseThomas A. BrogeTodd J. SuscovichDoris M. SnowMilan T. TomicGenevieve NonetKamaljit BajwaGuangyu ZhuZachary MartinezKyal HackettChristopher G. EarnhartNicole M. DorseySvetlana A. HopkinsDalia S. NatourHeather D. DavisMichael S. AndersonMelicia R. GaineyRonald R. CobbThe 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165815/?tool=EBI |
| spellingShingle | Robert V. House Thomas A. Broge Todd J. Suscovich Doris M. Snow Milan T. Tomic Genevieve Nonet Kamaljit Bajwa Guangyu Zhu Zachary Martinez Kyal Hackett Christopher G. Earnhart Nicole M. Dorsey Svetlana A. Hopkins Dalia S. Natour Heather D. Davis Michael S. Anderson Melicia R. Gainey Ronald R. Cobb Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics PLoS ONE |
| title | Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics |
| title_full | Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics |
| title_fullStr | Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics |
| title_full_unstemmed | Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics |
| title_short | Evaluation of strategies to modify Anti-SARS-CoV-2 monoclonal antibodies for optimal functionality as therapeutics |
| title_sort | evaluation of strategies to modify anti sars cov 2 monoclonal antibodies for optimal functionality as therapeutics |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165815/?tool=EBI |
| work_keys_str_mv | AT robertvhouse evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT thomasabroge evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT toddjsuscovich evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT dorismsnow evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT milanttomic evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT genevievenonet evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT kamaljitbajwa evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT guangyuzhu evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT zacharymartinez evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT kyalhackett evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT christophergearnhart evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT nicolemdorsey evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT svetlanaahopkins evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT daliasnatour evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT heatherddavis evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT michaelsanderson evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT meliciargainey evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics AT ronaldrcobb evaluationofstrategiestomodifyantisarscov2monoclonalantibodiesforoptimalfunctionalityastherapeutics |