Abstract
Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure.
Highlights
Effective deployment of multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines combined with aggressive vaccination campaigns have led to marked reductions in severe disease, hospitalizations, and death, including those caused by the variants of concern (Haas et al, 2021; Hall et al, 2021; Moghadas et al, 2020)
Passive immunization using anti-viral monoclonal antibody treatments may be an important tool for preventing breakthrough infections and mitigating immunopathological manifestations of coronavirus disease 2019 (COVID-19) in high-risk populations (Cohen et al, 2021)
Multiple studies have demonstrated that monoclonal antibody (mAb) targeting the receptor-binding domain (RBD) of the SARS-CoV-2 spike accelerate viral clearance in both preventative and therapeutic settings in rhesus models of COVID-19 (Baum et al, 2020; Shi et al, 2020; Zost et al, 2020; Kim et al, 2021)
Summary
Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. MAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARSCoV-2)-mediated stimulation of interferon-induced chemokines and T cell activation, significantly reducing development of interstitial pneumonia. MAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure
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