A Potent SARS-CoV-2 Neutralizing Human Monoclonal Antibody That Reduces Viral Burden and Disease Severity in Syrian Hamsters

Abstract

The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients.

SARS-CoV-2 infection, neuropathogenesis and transmission among deer mice: Implications for spillback to New World rodents

“…We have examined SARS-CoV-2 infection in Syrian hamsters using the same virus stock and dose described in this study [44]. While both Syrian hamsters and deer mice show bronchointerstitial pneumonia that is thought to be a significant reason for the severe COVID-19 in some human patients, total lung area affected in hamsters seems to be larger, precipitating respiratory clinical signs.…”

Live Imaging of SARS-CoV-2 Infection in Mice Reveals Neutralizing Antibodies Require Fc Function for Optimal Efficacy

“…Reporter-expressing viruses often purge foreign genes, particularly in vivo, due to fitness and immune pressure (Falzarano et al, 2014;Ventura et al, 2019). The ratio of copy numbers of SARS-CoV-2 nucleocapsid (N) to nLuc in the viral RNA by real-time PCR analyses of input virions and virions isolated from sera of mice at 6 dpi, however, remained unchanged (Figure 1I) indicating that the reporter was stable throughout the experimental timeline.…”

“…NAbs against the N-terminal domain (NTD) of S1 as well as the S2 subunit have also been isolated (Anand et al, 2021b;Liu et al, 2020;Voss et al, 2020). NAbs have demonstrated varying levels of efficacy and protection in multiple animal models of SARS-CoV-2 (Alsoussi et al, 2020;Baum et al, 2020;Fagre et al, 2020;Hansen et al, 2020;Hassan et al, 2020;Li et al, 2020;Rogers et al, 2020;Shi et al, 2020b;Winkler et al, 2020;Zost et al, 2020a;Zost et al, 2020b). However, the in vitro neutralization potency of NAbs has not consistently correlated with in vivo protection (Bournazos et al, 2014;Schafer et al, 2021).…”

A potently neutralizing anti-SARS-CoV-2 antibody inhibits variants of concern by binding a highly conserved epitope

“…Multiple effective vaccines against SARS-CoV-2 that prevent COVID-19 have been rapidly developed and deployed (Baden et al, 2021; Polack et al, 2020; Sadoff et al, 2021; Voysey et al, 2021). Monoclonal antibodies (mAb) also have shown efficacy in animal models of SARS-CoV-2 infection (Alsoussi et al, 2020; Baum et al, 2020a; Fagre et al, 2020; Hansen et al, 2020; Hassan et al, 2020; Kreye et al, 2020; Rogers et al, 2020; Shi et al, 2020; Zost et al, 2020), and two mAb treatments are approved for use in patients under Emergency Use Authorization (EUA) (Chen et al, 2021b; Weinreich et al, 2021). Therapy with mAbs may be beneficial to high-risk patients following exposure to SARS-CoV-2 with mild or moderate symptoms, but prior to onset of severe disease signs and symptoms, and can complement the usage of vaccines as a means of combating the COVID-19 pandemic.…”