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Summary: On November 24, 2021, the sequence of a new SARS-CoV-2 variant, Omicron-B.1.1.529, was announced. Compared to previous variants, Omicron has a higher number of mutations in the Spike (S) protein. Serum neutralization of Omicron by individuals vaccinated or previously infected with Alpha, Beta, Gamma, or Delta variants is significantly reduced or ineffective. Third vaccine doses can boost neutralization titers against Omicron, and high titers are observed in both vaccinated individuals and those infected with the Delta variant. Most potent monoclonal antibodies and antibodies under development are unable to effectively neutralize Omicron due to mutations in its Spike protein. Omicron has structural changes compared to earlier viruses and utilizes mutations that enhance its binding to ACE2, allowing for immune escape. This results in a large number of mutations in the ACE2 binding site and a rebalancing of receptor affinity similar to earlier pandemic viruses.
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Summary: The Omicron variant of SARS-CoV-2 has a higher affinity for ACE2 and can evade neutralizing antibodies more effectively compared to the Delta variant. A third dose of mRNA vaccine can provide enhanced protection. Omicron has lower replication in lung and gut cells and less efficiently cleaves its spike protein compared to Delta.
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Summary: The Omicron variant of SARS-CoV-2 has raised concerns due to its 37 amino acid substitutions in the spike protein, particularly in the receptor-binding domain (RBD), leading to increased binding affinity with human ACE2. Neutralizing activity against Omicron was greatly reduced in convalescent and vaccinated individuals compared to the ancestral virus, but this decrease was less significant after a third vaccine dose. Broadly neutralizing monoclonal antibodies recognizing conserved RBD epitopes may be crucial in combating the Omicron variant and future zoonotic transmissions.
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Summary: The B.1.1.529/Omicron variant of SARS-CoV-2, initially detected in southern Africa, has rapidly spread globally and is expected to become dominant due to its enhanced transmissibility in the coming weeks. This variant poses a threat to the efficacy of current COVID-19 vaccines and antibody therapies due to its significant antibody resistance. Even individuals who have received vaccines and booster doses may have reduced neutralizing activity against B.1.1.529.
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