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Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection from\n                    <jats:italic>orthoebolavirus zairense<\/jats:italic>\n                    (EBOV)\u2014one of three\n                    <jats:italic>orthoebolavirus<\/jats:italic>\n                    species that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies. Here, we describe a universal Ebola virus vaccine approach using a structure-guided design of candidates with hyperglycosylation that aims to direct antibody responses away from variable regions and toward conserved epitopes of GP. We first determined the hyperglycosylation landscape on Ebola virus GP and used that to generate hyperglycosylated GP variants with two to four additional glycosylation sites to mask the highly variable glycan cap region. We then created vaccine candidates by displaying wild-type or hyperglycosylated GP variants on ferritin nanoparticles (Fer). Immunization with these antigens elicited potent neutralizing antisera against EBOV in mice. Importantly, we observed consistent cross-neutralizing activity against Bundibugyo virus and Sudan virus from hyperglycosylated GP-Fer with two or three additional glycans. In comparison, elicitation of cross-neutralizing antisera was rare in mice immunized with wild-type GP-Fer. These results demonstrate a potential strategy to develop universal Ebola virus vaccines that confer cross-protective immunity against existing and emerging filovirus species.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2316960121","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T13:36:19Z","timestamp":1707226579000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":24,"title":["Design of universal Ebola virus vaccine candidates via immunofocusing"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0483-8719","authenticated-orcid":false,"given":"Duo","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail E.","family":"Powell","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Utz","sequence":"additional","affiliation":[{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"},{"name":"Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Stanford Biophysics Program, Stanford University School of Medicine, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1365-4279","authenticated-orcid":false,"given":"Mrinmoy","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Do","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9770-7525","authenticated-orcid":false,"given":"J. J.","family":"Patten","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118"},{"name":"Department of Virology, Immunology, and Microbiology, Boston University School of Medicine, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan I.","family":"Moliva","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118"},{"name":"Department of Virology, Immunology, and Microbiology, Boston University School of Medicine, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy J.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118"},{"name":"Department of Virology, Immunology, and Microbiology, Boston University School of Medicine, Boston, MA 02118"},{"name":"Department of Biology, Boston University, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9168-2892","authenticated-orcid":false,"given":"Robert A.","family":"Davey","sequence":"additional","affiliation":[{"name":"National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118"},{"name":"Department of Virology, Immunology, and Microbiology, Boston University School of Medicine, Boston, MA 02118"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6503-4541","authenticated-orcid":false,"given":"Peter S.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305"},{"name":"Sarafan ChEM-H, Stanford University, Stanford, CA 94305"},{"name":"Chan Zuckerberg Biohub, San Francisco, CA 94158"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,2,6]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)33132-5"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-015-0480-y"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-020-0147-3"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1901594"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010078"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414216"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1473698"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2201.151410"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32621-6"},{"key":"e_1_3_4_10_2","unstructured":"First FDA-approved vaccine for the prevention of Ebola virus disease marking a critical milestone in public health preparedness and response (2019). https:\/\/www.fda.gov\/news-events\/press-announcements\/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health. 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