[ { "id": "authors:naz36-42m36", "collection": "authors", "collection_id": "naz36-42m36", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220705-214139631", "type": "article", "title": "Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models", "author": [ { "family_name": "Cohen", "given_name": "Alexander A.", "orcid": "0000-0002-2818-656X", "clpid": "Cohen-Alexander-A" }, { "family_name": "van Doremalen", "given_name": "Neeltje", "orcid": "0000-0003-4368-6359", "clpid": "van-Doremalen-Neeltje-A" }, { "family_name": "Greaney", "given_name": "Allison J.", "orcid": "0000-0001-7202-3349", "clpid": "Greaney-Allison-J" }, { "family_name": "Andersen", "given_name": "Hanne", "orcid": "0000-0003-1103-9608", "clpid": "Andersen-Hanne" }, { "family_name": "Sharma", "given_name": "Ankur", "clpid": "Sharma-Ankur" }, { "family_name": "Starr", "given_name": "Tyler N.", "orcid": "0000-0001-6713-6904", "clpid": "Starr-Tyler-N" }, { "family_name": "Keeffe", "given_name": "Jennifer R.", "orcid": "0000-0002-5317-6398", "clpid": "Keeffe-Jennifer-R" }, { "family_name": "Fan", "given_name": "Chengcheng", "orcid": "0000-0003-4213-5758", "clpid": "Fan-Chengcheng" }, { "family_name": "Schulz", "given_name": "Jonathan E.", "orcid": "0000-0001-5462-5952", "clpid": "Schulz-Jonathan-E" }, { "family_name": "Gnanapragasam", "given_name": "Priyanthi N. P.", "clpid": "Gnanapragasam-Priyanthi-N-P" }, { "family_name": "Kakutani", "given_name": "Leesa M.", "orcid": "0000-0003-3822-7449", "clpid": "Kakutani-Leesa-M" }, { "family_name": "West", "given_name": "Anthony P., Jr.", "orcid": "0000-0003-4213-5184", "clpid": "West-Anthony-P-Jr" }, { "family_name": "Saturday", "given_name": "Greg", "orcid": "0000-0002-0803-6177", "clpid": "Saturday-Greg" }, { "family_name": "Lee", "given_name": "Yu E.", "orcid": "0000-0001-5989-326X", "clpid": "Lee-Yu-Erica" }, { "family_name": "Gao", "given_name": "Han", "clpid": "Gao-Han" }, { "family_name": "Jette", "given_name": "Claudia A.", "orcid": "0000-0002-5085-8027", "clpid": "Jette-Claudia-A" }, { "family_name": "Lewis", "given_name": "Mark G.", "orcid": "0000-0001-7852-0135", "clpid": "Lewis-Mark-G" }, { "family_name": "Tan", "given_name": "Tiong K.", "orcid": "0000-0001-8746-8308", "clpid": "Tan-Tiong-K" }, { "family_name": "Townsend", "given_name": "Alain R.", "orcid": "0000-0002-3702-0107", "clpid": "Townsend-Alain-R" }, { "family_name": "Bloom", "given_name": "Jesse D.", "orcid": "0000-0003-1267-3408", "clpid": "Bloom-Jesse-D" }, { "family_name": "Munster", "given_name": "Vincent J.", "orcid": "0000-0002-2288-3196", "clpid": "Munster-Vincent-J" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" } ], "abstract": "To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.", "doi": "10.1126/science.abq0839", "pmcid": "PMC9273039", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2022-08-05", "series_number": "6606", "volume": "377", "issue": "6606", "pages": "Art. No. eabq0839" }, { "id": "authors:p1p7m-9mv98", "collection": "authors", "collection_id": "p1p7m-9mv98", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210322-133440105", "type": "article", "title": "Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies", "author": [ { "family_name": "Greaney", "given_name": "Allison J.", "orcid": "0000-0001-7202-3349", "clpid": "Greaney-Allison-J" }, { "family_name": "Starr", "given_name": "Tyler N.", "orcid": "0000-0001-6713-6904", "clpid": "Starr-Tyler-N" }, { "family_name": "Barnes", "given_name": "Christopher O.", "orcid": "0000-0003-2754-5951", "clpid": "Barnes-Christopher-O" }, { "family_name": "Weisblum", "given_name": "Yiska", "orcid": "0000-0002-9249-1745", "clpid": "Weisblum-Yiska" }, { "family_name": "Schmidt", "given_name": "Fabian", "clpid": "Schmidt-Fabian" }, { "family_name": "Caskey", "given_name": "Marina", "orcid": "0000-0003-1727-8693", "clpid": "Caskey-Marina" }, { "family_name": "Gaebler", "given_name": "Christian", "orcid": "0000-0001-7295-8128", "clpid": "Gaebler-Christian" }, { "family_name": "Cho", "given_name": "Alice", "orcid": "0000-0001-6354-6148", "clpid": "Cho-Alice" }, { "family_name": "Agudelo", "given_name": "Marianna", "orcid": "0000-0003-3924-6449", "clpid": "Agudelo-Marianna" }, { "family_name": "Finkin", "given_name": "Shlomo", "orcid": "0000-0003-4474-2658", "clpid": "Finkin-Shlomo" }, { "family_name": "Wang", "given_name": "Zijun", "orcid": "0000-0002-2095-2151", "clpid": "Wang-Zijun" }, { "family_name": "Poston", "given_name": "Daniel", "clpid": "Poston-Daniel" }, { "family_name": "Muecksch", "given_name": "Frauke", "clpid": "Muecksch-Frauke" }, { "family_name": "Hatziioannou", "given_name": "Theodora", "orcid": "0000-0002-7889-0766", "clpid": "Hatziioannou-Theodora" }, { "family_name": "Bieniasz", "given_name": "Paul D.", "orcid": "0000-0002-2368-3719", "clpid": "Bieniasz-Paul-D" }, { "family_name": "Robbiani", "given_name": "Davide F.", "orcid": "0000-0001-7379-3484", "clpid": "Robbiani-Davide-F" }, { "family_name": "Nussenzweig", "given_name": "Michel C.", "orcid": "0000-0003-0592-8564", "clpid": "Nussenzweig-Michel-C" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Bloom", "given_name": "Jesse D.", "orcid": "0000-0003-1267-3408", "clpid": "Bloom-Jesse-D" } ], "abstract": "Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.", "doi": "10.1038/s41467-021-24435-8", "pmcid": "PMC8263750", "issn": "2041-1723", "publisher": "Nature Publishing Group", "publication": "Nature Communications", "publication_date": "2021-07-07", "volume": "12", "pages": "Art. No. 4196" }, { "id": "authors:40sg9-d3h73", "collection": "authors", "collection_id": "40sg9-d3h73", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210513-115757419", "type": "article", "title": "Investigate the origins of COVID-19", "author": [ { "family_name": "Bloom", "given_name": "Jesse D.", "orcid": "0000-0003-1267-3408", "clpid": "Bloom-Jesse-D" }, { "family_name": "Chan", "given_name": "Yujia Alina", "clpid": "Chan-Yujia-Alina" }, { "family_name": "Baric", "given_name": "Ralph S.", "clpid": "Baric-Ralph-S" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Cobey", "given_name": "Sarah", "clpid": "Cobey-Sarah" }, { "family_name": "Deverman", "given_name": "Benjamin E.", "orcid": "0000-0002-6223-9303", "clpid": "Deverman-Benjamin-E" }, { "family_name": "Fisman", "given_name": "David N.", "clpid": "Fisman-David-N" }, { "family_name": "Gupta", "given_name": "Ravindra", "clpid": "Gupta-Ravindra" }, { "family_name": "Iwasaki", "given_name": "Akiko", "clpid": "Iwasaki-Akiko" }, { "family_name": "Lipsitch", "given_name": "Marc", "clpid": "Lipsitch-Marc" }, { "family_name": "Medzhitov", "given_name": "Ruslan", "clpid": "Medzhitov-Ruslan" }, { "family_name": "Neher", "given_name": "Richard A.", "clpid": "Neher-Richard-A" }, { "family_name": "Nielsen", "given_name": "Rasmus", "clpid": "Nielsen-Rasmus" }, { "family_name": "Patterson", "given_name": "Nick", "clpid": "Patterson-Nick" }, { "family_name": "Stearns", "given_name": "Tim", "clpid": "Stearns-Tim" }, { "family_name": "van Nimwegen", "given_name": "Erik", "clpid": "van-Nimwegen-Erik" }, { "family_name": "Worobey", "given_name": "Michael", "clpid": "Worobey-Michael" }, { "family_name": "Relman", "given_name": "David A.", "clpid": "Relman-David-A" } ], "abstract": "On 30 December 2019, the Program for Monitoring Emerging Diseases notified the world about a pneumonia of unknown cause in Wuhan, China (1). Since then, scientists have made remarkable progress in understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogenesis, and mitigation by vaccines, therapeutics, and non-pharmaceutical interventions. Yet more investigation is still needed to determine the origin of the pandemic. Theories of accidental release from a lab and zoonotic spillover both remain viable. Knowing how COVID-19 emerged is critical for informing global strategies to mitigate the risk of future outbreaks.", "doi": "10.1126/science.abj0016", "pmcid": "PMC9520851", "issn": "0036-8075", "publisher": "American Association for the Advancement of Science", "publication": "Science", "publication_date": "2021-05-14", "series_number": "6543", "volume": "372", "issue": "6543", "pages": "694" }, { "id": "authors:da6gc-y2604", "collection": "authors", "collection_id": "da6gc-y2604", "cite_using_url": "https://resolver.caltech.edu/CaltechAUTHORS:20200130-110348875", "type": "article", "title": "Restriction of HIV-1 Escape by a Highly Broad and Potent Neutralizing Antibody", "author": [ { "family_name": "Schommers", "given_name": "Philipp", "orcid": "0000-0003-3375-6800", "clpid": "Schommers-Philipp" }, { "family_name": "Gruell", "given_name": "Henning", "clpid": "Gruell-Henning" }, { "family_name": "Abernathy", "given_name": "Morgan E.", "clpid": "Abernathy-Morgan-E" }, { "family_name": "Tran", "given_name": "My-Kim", "clpid": "Tran-My-Kim" }, { "family_name": "Dingens", "given_name": "Adam S.", "clpid": "Dingens-Adam-S" }, { "family_name": "Gristick", "given_name": "Harry B.", "orcid": "0000-0002-1957-2821", "clpid": "Gristick-Harry-B" }, { "family_name": "Barnes", "given_name": "Christopher O.", "orcid": "0000-0003-2754-5951", "clpid": "Barnes-Christopher-O" }, { "family_name": "Schoofs", "given_name": "Till", "clpid": "Schoofs-Till" }, { "family_name": "Schlotz", "given_name": "Maike", "clpid": "Schlotz-Maike" }, { "family_name": "Vanshylla", "given_name": "Kanika", "clpid": "Vanshylla-Kanika" }, { "family_name": "Kreer", "given_name": "Christoph", "clpid": "Kreer-Christoph" }, { "family_name": "Weiland", "given_name": "Daniela", "clpid": "Weiland-Daniela" }, { "family_name": "Holtick", "given_name": "Udo", "clpid": "Holtick-Udo" }, { "family_name": "Scheid", "given_name": "Christof", "clpid": "Scheid-Christof" }, { "family_name": "Valter", "given_name": "Markus M.", "clpid": "Valter-Markus-M" }, { "family_name": "van Gils", "given_name": "Marit J.", "clpid": "van-Gils-Marit-J" }, { "family_name": "Sanders", "given_name": "Rogier W.", "clpid": "Sanders-Rogier-W" }, { "family_name": "Vehreschild", "given_name": "J\u00f6rg J.", "clpid": "Vehreschild-J\u00f6rg-J" }, { "family_name": "Cornely", "given_name": "Oliver A.", "clpid": "Cornely-Oliver-A" }, { "family_name": "Lehmann", "given_name": "Clara", "clpid": "Lehmann-Clara" }, { "family_name": "F\u00e4tkenheuer", "given_name": "Gerd", "clpid": "F\u00e4tkenheuer-Gerd" }, { "family_name": "Seaman", "given_name": "Michael S.", "clpid": "Seaman-Michael-S" }, { "family_name": "Bloom", "given_name": "Jesse D.", "orcid": "0000-0003-1267-3408", "clpid": "Bloom-Jesse-D" }, { "family_name": "Bjorkman", "given_name": "Pamela J.", "orcid": "0000-0002-2277-3990", "clpid": "Bjorkman-P-J" }, { "family_name": "Klein", "given_name": "Florian", "orcid": "0000-0003-1376-1792", "clpid": "Klein-Florian" } ], "abstract": "Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new V_H1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC\u2085\u2080 = 0.048 \u03bcg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-\u00c5 cryo-EM structure of a 1-18-BG505_(SOSIP.664) Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.", "doi": "10.1016/j.cell.2020.01.010", "pmcid": "PMC7042716", "issn": "0092-8674", "publisher": "Cell Press", "publication": "Cell", "publication_date": "2020-02-06", "series_number": "3", "volume": "180", "issue": "3", "pages": "471-489" } ]