Novel antibodies target human receptors to neutralize SARS-CoV-2 variants and future sarbecoviruses NatureMicrobiol antibodies covid COVID19 SARSCoV2 variants sarbecovirus monoclonalantibodies
By Neha MathurMay 17 2023Reviewed by Lily Ramsey, LLM In a recent study published in the Nature Microbiology Journal, researchers generated six human monoclonal antibodies that prevented infection by all human angiotensin-converting enzyme 2 binding sarbecoviruses tested, including severe acute respiratory syndrome coronavirus 2 and its variants, Delta and Omicron.
Any new S-targeting mAb therapy will also probably have limited utility because SARS-CoV-2 will continue to adapt to human antibodies. Ideally, mAbs developed in anticipation of future pandemics caused by sarbecoviruses should be resilient to mutations that arise in them. Further, the team generated hybridomas from mice using sera that inhibited SARS-CoV-2 pseudotyped viruses. They used enzyme-linked immunosorbent assay to screen hybridoma supernatants for hACE2-binding mAbs.
They used single-particle cryo-electron microscopy to delineate the structural basis for broad neutralization of anti-hACE2 mAbs. These ten mAbs were 1C9H1, 4A12A4, 05B04, 2C12H3, 2F6A6, 2G7A1, 05D06, 05E10, 05G01 and 05H02. Four of the five mAbs from the KP AlivaMab mice, viz., 05B04, 05E10, 05G01, and 05D06, shared identical complementarity-determining regions . Conversely, AV AlivaMab mice-derived mAbs were diverse.
In addition, the anti-hACE2 mAbs showed favorable pharmacokinetics and no ill effects on the hACE2 knock-in mice. When used prophylactically in hACE2 knock-in mice, these mAbs conferred near-sterilizing protection against lung SARS-CoV-2 infection.The six anti-hACE2 mAbs also inhibited infection by pseudotyped SARS-CoV-2 variants, Delta, and Omicron, with similar potency, i.e., half maximal inhibitory concentration values ranging between 8.2 ng ml−1 and 197 ng ml−1.
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