Characterization of cross‐reactive monoclonal antibodies against SARS‐CoV‐1 and SARS‐CoV‐2: Implication for rational design and development of pan‐sarbecovirus vaccines and neutralizing antibodies

Abstract

Emergence of various circulating SARS‐CoV‐2 variants of concern (VOCs) promotes the identification of pan‐sarbecovirus vaccines and broadly neutralizing antibodies (bNAbs). Here, to characterize monoclonal antibodies cross‐reactive against both SARS‐CoV‐1 and SARS‐CoV‐2 and to search the criterion for bNAbs against all emerging SARS‐CoV‐2, we isolated several SARS‐CoV‐1‐cross‐reactive monoclonal antibodies (mAbs) from a wildtype SARS‐CoV‐2 convalescent donor. These antibodies showed broad binding capacity and cross‐neutralizing potency against various SARS‐CoV‐2 VOCs, including B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), and B.1.617.2 (Delta), but failed to efficiently neutralize Omicron variant and its sublineages. Structural analysis revealed how Omicron sublineages, but not other VOCs, efficiently evade an antibody family cross‐reactive against SARS‐CoV‐1 through their escape mutations. Further evaluation of a series of SARS‐CoV‐1/2‐cross‐reactive bNAbs showed a negative correlation between the neutralizing activities against SARS‐CoV‐1 and SARS‐CoV‐2 Omicron variant. Together, these results suggest the necessity of using cross‐neutralization against SARS‐CoV‐1 and SARS‐CoV‐2 Omicron as criteria for rational design and development of potent pan‐sarbecovirus vaccines and bNAbs.

The epidemiological and clinical characteristics of COVID‐19 patients admitted to a Fangcang shelter hospital in Beijing before the change in China's prevention and control policy

“…Mild case: (1) positive for SARS-CoV-2 by RT-PCR Or positive for IgG and IgM antibody in non-vaccinated cases; (2) mild clinical symptoms and still exist at the time of admission to Fangcang shelter hospital.…”

“…Since the outbreak of the COVID‐19 epidemic at the end of 2019, the world has experienced several major outbreaks caused by different variants of concern (VOCs) 1 . Although COVID‐19 vaccines were developed rapidly and the vaccination was actively advocated for, constant viral mutations affected the efficacy of approved vaccines 2 .…”

“…Since the outbreak of the COVID-19 epidemic at the end of 2019, the world has experienced several major outbreaks caused by different variants of concern (VOCs). 1 Although COVID-19 vaccines were developed rapidly and the vaccination was actively advocated for, constant viral mutations affected the efficacy of approved vaccines. 2 The infectivity and immune escape ability of SARS-CoV-2 variants constantly changed, which caused different disease characteristics in the epidemic dominated by the original strain to the Omicron variant, and the Omicron variant had higher infectivity and immune escape ability.…”