Broadly neutralizing antibodies targeting a conserved silent face of spike RBD resist extreme SARS-CoV-2 antigenic drift.

Autor:	Song G; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Yuan M; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Liu H; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Capozzola T; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Lin RN; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Torres JL; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., He WT; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Musharrafieh R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Dueker K; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Zhou P; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Callaghan S; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Mishra N; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Yong P; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Anzanello F; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Avillion G; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Vo AL; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Li X; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Makhdoomi M; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Feng Z; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Zhu X; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Peng L; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Nemazee D; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Safonova Y; Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA., Briney B; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA., Ward AB; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Burton DR; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA., Wilson IA; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.; Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA., Andrabi R; Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.; IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, CA 92037, USA.; Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.; Lead Contact.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Apr 27. Date of Electronic Publication: 2023 Apr 27.
DOI:	10.1101/2023.04.26.538488
Abstrakt:	Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline-encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized "site V" on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV-2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites. Competing Interests: Declaration of interests G.S., W.H., P.Z., S.C., R.M., K.D., D.R.B. and R.A. are listed as inventors on pending patent applications describing the betacoronavirus broadly neutralizing antibodies. All other authors have no competing interests to declare.
Databáze:	MEDLINE
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