tetano
Editor, Senior Moderator
Front Cell Infect Microbiol
. 2021 Nov 18;11:753444.
doi: 10.3389/fcimb.2021.753444. eCollection 2021.
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies
Brandon J Beddingfield[SUP] 1 [/SUP], Nicholas J Maness[SUP] 1 2 [/SUP], Alyssa C Fears[SUP] 1 [/SUP], Jay Rappaport[SUP] 2 3 [/SUP], Pyone Pyone Aye[SUP] 3 [/SUP], Kasi Russell-Lodrigue[SUP] 4 [/SUP], Lara A Doyle-Meyers[SUP] 4 [/SUP], Robert V Blair[SUP] 3 [/SUP], Ann M Carias[SUP] 5 [/SUP], Patrick J Madden[SUP] 5 [/SUP], Ramon Lorenzo Redondo[SUP] 5 [/SUP], Hongmei Gao[SUP] 6 [/SUP], David Montefiori[SUP] 6 7 [/SUP], Thomas J Hope[SUP] 5 [/SUP], Chad J Roy[SUP] 1 2 [/SUP]
Affiliations
Abstract
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.
Keywords: SARS-CoV-2; SARS-CoV-2 antibodies; immunoprophylaxis; nonhuman primates; pharmacokinetics.
. 2021 Nov 18;11:753444.
doi: 10.3389/fcimb.2021.753444. eCollection 2021.
Effective Prophylaxis of COVID-19 in Rhesus Macaques Using a Combination of Two Parenterally-Administered SARS-CoV-2 Neutralizing Antibodies
Brandon J Beddingfield[SUP] 1 [/SUP], Nicholas J Maness[SUP] 1 2 [/SUP], Alyssa C Fears[SUP] 1 [/SUP], Jay Rappaport[SUP] 2 3 [/SUP], Pyone Pyone Aye[SUP] 3 [/SUP], Kasi Russell-Lodrigue[SUP] 4 [/SUP], Lara A Doyle-Meyers[SUP] 4 [/SUP], Robert V Blair[SUP] 3 [/SUP], Ann M Carias[SUP] 5 [/SUP], Patrick J Madden[SUP] 5 [/SUP], Ramon Lorenzo Redondo[SUP] 5 [/SUP], Hongmei Gao[SUP] 6 [/SUP], David Montefiori[SUP] 6 7 [/SUP], Thomas J Hope[SUP] 5 [/SUP], Chad J Roy[SUP] 1 2 [/SUP]
Affiliations
- PMID: 34869063
- PMCID: PMC8637877
- DOI: 10.3389/fcimb.2021.753444
Abstract
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.
Keywords: SARS-CoV-2; SARS-CoV-2 antibodies; immunoprophylaxis; nonhuman primates; pharmacokinetics.