Effective prophylaxis of COVID-19 in rhesus macaques using a combination of two parentally-administered SARS-CoV-2 neutralizing antibodies

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.

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

“…SARS-CoV-2 infection in the non-human primate (NHP), rhesus macaques ( Macaca mulatta ), recapitulates mild to moderate human disease 16–18 . Infected macaques exhibit viral shedding through the respiratory tract and viral pneumonia similar to the mild form seen in humans.…”

“…To gain critical insights into systemic infection by SARS-CoV-2, new animal models are needed to determine the extent of disseminated infection and its relationship to pathogenesis. SARS-CoV-2 infection in the non-human primate (NHP), rhesus macaques (Macaca mulatta), recapitulates mild to moderate human disease [16][17][18] . Infected macaques exhibit viral shedding through the respiratory tract and viral pneumonia similar to the mild form seen in humans.…”

Immunobiology of COVID-19: Mechanistic and therapeutic insights from animal models

“…The effects of different modes of vaccine delivery on immune efficacy have also been verified in animal models. In addition to traditional intramuscular injection, oral (Beddingfield et al, 2021;Langel et al, 2022;Yu et al, 2022b) and intranasal vaccines (Langel et al, 2022;Sui et al, 2021b;Tokunoh et al, 2023) have also been shown to provide protection. These animal models have significantly enhanced our understanding of the immune protective mechanisms against SARS-CoV-2 (Figure 2).…”

The pigtail macaque (Macaca nemestrina) model of COVID-19 reproduces diverse clinical outcomes and reveals new and complex signatures of disease

“…Viral RNA Quantification by Quantitative Real-Time PCR Quantification of viral RNA was performed as described22 using the CDC N1 primers/probe for quantification of total viral RNA and with primers/probe specific for the nucleocapsid subgenomic RNA to provide an estimate of replicating virus. Specifically, vRNA was quantified using the QuantStudio 6 Real-Time PCR System (Applied Biosystems, Waltham, MA).…”