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Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections2,3. Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles4,5, and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants.
Pubmed ID: 36535326
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THIS RESOURCE IS NO LONGER IN SERVICE.Documented on January 4,2023. IgBLAST was developed at NCBI to facilitate analysis of immunoglobulin V region sequences in GenBank. In addition to performing a regular BLAST search, IgBLAST has several additional functions: - Reports the germline V, D and J gene matches to the query sequence. - Annotates the immunoglobulin domains (FWR1 through FWR3). - Matches the returned hits (for databases other than germline genes) to the closest germline V genes, making it easier to identify related sequences. - Reveals the V(D)J junction details such as nucleotide homology between the ends of V(D)J segments and N nucleotide insertions. D and J gene reporting is only for nucleotide sequence search and requires a stretch of five or more nucleotide identity between the query and D or J genes. Sponsors: This resource is supported by the National Center for Biotechnology Information, a division of the U.S. National Library of Medicine.
View all literature mentionsCommercial organization which provides life science services and products to researchers. They specialize in gene synthesis, peptide, protein, antibody and preclinical drug development service.
View all literature mentionsBiopython is a set of freely available tools for biological computation written in Python by an international team of developers. It is a distributed collaborative effort to develop Python libraries and applications which address the needs of current and future work in bioinformatics. The source code is made available under the Biopython License, which is extremely liberal and compatible with almost every license in the world. It works along with the Open Bioinformatics Foundation, who generously host it''s website, bug tracker, and mailing lists. Sponsor: This resource is supported by the Open Bioinformatics Foundation. Keywords: Tool, Software, Python, Biological, Computation, Bioinformatics,
View all literature mentionsA Python-based environment of open-source software for mathematics, science, and engineering. The core packages of SciPy include: NumPy, a base N-dimensional array package; SciPy Library, a fundamental library for scientific computing; and IPython, an enhanced interactive console.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsOpen source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.
View all literature mentionsCell line Huh-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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