Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies
SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-C...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/9bf5b7e52088482b9bde993ef28f1d7d |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:9bf5b7e52088482b9bde993ef28f1d7d |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:9bf5b7e52088482b9bde993ef28f1d7d2021-11-18T09:56:06ZEffective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies2235-298810.3389/fcimb.2021.753444https://doaj.org/article/9bf5b7e52088482b9bde993ef28f1d7d2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.753444/fullhttps://doaj.org/toc/2235-2988SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination.Brandon J. BeddingfieldNicholas J. ManessNicholas J. ManessAlyssa C. FearsJay RappaportJay RappaportPyone Pyone AyeKasi Russell-LodrigueLara A. Doyle-MeyersRobert V. BlairAnn M. CariasPatrick J. MaddenRamon Lorenzo RedondoHongmei GaoDavid MontefioriDavid MontefioriThomas J. HopeChad J. RoyChad J. RoyFrontiers Media S.A.articleSARS-CoV-2SARS-CoV-2 antibodiesnonhuman primatesimmunoprophylaxispharmacokineticsMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
SARS-CoV-2 SARS-CoV-2 antibodies nonhuman primates immunoprophylaxis pharmacokinetics Microbiology QR1-502 |
| spellingShingle |
SARS-CoV-2 SARS-CoV-2 antibodies nonhuman primates immunoprophylaxis pharmacokinetics Microbiology QR1-502 Brandon J. Beddingfield Nicholas J. Maness Nicholas J. Maness Alyssa C. Fears Jay Rappaport Jay Rappaport Pyone Pyone Aye Kasi Russell-Lodrigue Lara A. Doyle-Meyers Robert V. Blair Ann M. Carias Patrick J. Madden Ramon Lorenzo Redondo Hongmei Gao David Montefiori David Montefiori Thomas J. Hope Chad J. Roy Chad J. Roy Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies |
| description |
SARS-CoV-2 is a respiratory borne pathogenic beta coronavirus that is the source of a worldwide pandemic and the cause of multiple pathologies in man. The rhesus macaque model of COVID-19 was utilized to test the added benefit of combinatory parenteral administration of two high-affinity anti-SARS-CoV-2 monoclonal antibodies (mAbs; C144-LS and C135-LS) expressly developed to neutralize the virus and modified to extend their pharmacokinetics. After completion of kinetics study of mAbs in the primate, combination treatment was administered prophylactically to mucosal viral challenge. Results showed near complete virus neutralization evidenced by no measurable titer in mucosal tissue swabs, muting of cytokine/chemokine response, and lack of any discernable pathologic sequalae. Blocking infection was a dose-related effect, cohorts receiving lower doses (6, 2 mg/kg) resulted in low grade viral infection in various mucosal sites compared to that of a fully protective dose (20 mg/kg). A subset of animals within this cohort whose infectious challenge was delayed 75 days later after mAb administration were still protected from disease. Results indicate this combination mAb effectively blocks development of COVID-19 in the rhesus disease model and accelerates the prospect of clinical studies with this effective antibody combination. |
| format |
article |
| author |
Brandon J. Beddingfield Nicholas J. Maness Nicholas J. Maness Alyssa C. Fears Jay Rappaport Jay Rappaport Pyone Pyone Aye Kasi Russell-Lodrigue Lara A. Doyle-Meyers Robert V. Blair Ann M. Carias Patrick J. Madden Ramon Lorenzo Redondo Hongmei Gao David Montefiori David Montefiori Thomas J. Hope Chad J. Roy Chad J. Roy |
| author_facet |
Brandon J. Beddingfield Nicholas J. Maness Nicholas J. Maness Alyssa C. Fears Jay Rappaport Jay Rappaport Pyone Pyone Aye Kasi Russell-Lodrigue Lara A. Doyle-Meyers Robert V. Blair Ann M. Carias Patrick J. Madden Ramon Lorenzo Redondo Hongmei Gao David Montefiori David Montefiori Thomas J. Hope Chad J. Roy Chad J. Roy |
| author_sort |
Brandon J. Beddingfield |
| title |
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies |
| title_short |
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies |
| title_full |
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies |
| title_fullStr |
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies |
| title_full_unstemmed |
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies |
| title_sort |
effective prophylaxis of covid-19 in rhesus macaques using a combination of two parenterally-administered sars-cov-2 neutralizing antibodies |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/9bf5b7e52088482b9bde993ef28f1d7d |
| work_keys_str_mv |
AT brandonjbeddingfield effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT nicholasjmaness effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT nicholasjmaness effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT alyssacfears effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT jayrappaport effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT jayrappaport effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT pyonepyoneaye effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT kasirusselllodrigue effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT laraadoylemeyers effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT robertvblair effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT annmcarias effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT patrickjmadden effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT ramonlorenzoredondo effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT hongmeigao effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT davidmontefiori effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT davidmontefiori effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT thomasjhope effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT chadjroy effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies AT chadjroy effectiveprophylaxisofcovid19inrhesusmacaquesusingacombinationoftwoparenterallyadministeredsarscov2neutralizingantibodies |
| _version_ |
1718420859820965888 |