{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:33Z","timestamp":1787005773072,"version":"build-2736575974"},"reference-count":63,"publisher":"National Academy of Sciences","issue":"25","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5SC1GM139701"],"award-info":[{"award-number":["5SC1GM139701"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5G12MD007603-30"],"award-info":[{"award-number":["5G12MD007603-30"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000893","name":"Simons Foundation","doi-asserted-by":"publisher","award":["349247"],"award-info":[{"award-number":["349247"]}],"id":[{"id":"10.13039\/100000893","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM103310"],"award-info":[{"award-number":["GM103310"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100023520","name":"DOD | Department of Defense Education Activity","doi-asserted-by":"publisher","award":["W81XH19C0169"],"award-info":[{"award-number":["W81XH19C0169"]}],"id":[{"id":"10.13039\/100023520","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,6,23]]},"abstract":"<jats:p>Adenoviridae family members routinely infect humans, exhibit significant genetic diversity, and are associated with a variety of illnesses. Types 4 and 7 frequently circulate in the United States and are major causes of respiratory disease. Infections can result in hospitalization and, in severe cases, death. Although a live wild-type-virus vaccine targeting these two types exists, its use is restricted to military personnel due to concerns about viral-shedding and potential for genetic recombination. To overcome these limitations, we recently developed a virus-like particle (VLP) platform as an alternative vaccination strategy. These VLPs are stable, lack genomic material, and elicit a potent humoral immune response in mice, effectively neutralizing adenoviral infection. Here, we describe the cryo-EM structure of adenovirus 7 (AdV-7) VLPs. Structural insights are essential to ensure that neutralizing antigens displayed on the VLPs accurately mimic those of the virion, guide the design of particles with improved stability and efficacy, and enable engineering of VLPs with antigenic properties targeting multiple adenovirus types. The structure shows that hexon, penton, pIIIa, pVI, pVIII, and IX assemble comparable to AdV-5, hexon and penton neutralizing epitopes are appropriately displayed for antibody recognition, penton insertion into the hexon shell promotes cement protein pIIIa to increase its interaction with the peripentonal hexons, and presence of the core-genome is associated with increased interaction between cement protein pVIII and hexon. Finally, limited proteolysis and mass spectrometry demonstrate that VLP incorporated hexons digest more readily than virion incorporated hexons, indicating the greater dynamic nature of the VLP.<\/jats:p>","DOI":"10.1073\/pnas.2526969123","type":"journal-article","created":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:16:51Z","timestamp":1781626611000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["Structure of Human adenovirus 7 virus-like particles, a platform for developing nanotherapeutics and studying capsid assembly"],"prefix":"10.1073","volume":"123","author":[{"given":"Kiyano","family":"Madoo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry and Biochemistry, The City College of New York at The City University of New York","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Mazboudi","sequence":"additional","affiliation":[{"name":"TechnoVax, Inc.","place":["Kinnelon"]},{"name":"Biotherapeutics Discovery, Boehringer-Ingelheim Pharmaceutical Inc.","place":["Ridgefield"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4377-2830","authenticated-orcid":false,"given":"Zubaida Marufee","family":"Islam","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Department, Queens College of The City University of New York","place":["Flushing"]},{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Doctoral Program, The Graduate Center of The City University of New York","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-8658","authenticated-orcid":false,"given":"Jonathan","family":"Luo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Department, Queens College of The City University of New York","place":["Flushing"]},{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Doctoral Program, The Graduate Center of The City University of New York","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Kuschner","sequence":"additional","affiliation":[{"name":"Capsidvax","place":["Arlington"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-2732","authenticated-orcid":false,"given":"Paul","family":"Gottlieb","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"City University of New York School of Medicine, The City College of New York","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-4529","authenticated-orcid":false,"given":"John J.","family":"Dennehy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Department, Queens College of The City University of New York","place":["Flushing"]},{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Biology Doctoral Program, The Graduate Center of The City University of New York","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rinat R.","family":"Abzalimov","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Structural Biology Initiative, City University of New York Advanced Science Research Center","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4661-509X","authenticated-orcid":false,"given":"Jose M.","family":"Galarza","sequence":"additional","affiliation":[{"name":"TechnoVax, Inc.","place":["Kinnelon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6601-2184","authenticated-orcid":false,"given":"Reza","family":"Khayat","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00453a208","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry and Biochemistry, The City College of New York at The City University of New York","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-84-20714"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.3181\/00379727-85-20825"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.001721"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2011.04.031"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2021.08.009"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00116-13"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9071(199607)49:3<170::AID-JMV3>3.0.CO;2-1"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.2095"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/338471"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.20087"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1803.111238"},{"key":"e_1_3_4_12_2","unstructured":"S. Elnahal NJDOH confirms 11th pediatric death of Wanaque patient; Commissioner requests MRC volunteers to speed up separation of patients. NJ Department of Health (2018). https:\/\/www.nj.gov\/health\/news\/2018\/20181116a.shtml. Accessed 16 November 2018."},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2105\/AJPH.55.1.38"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/milmed\/160.6.300"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/124.2.148"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines8030411"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep01812"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-023-00754-3"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41478-1"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01453-15"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abe0974"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00850-17"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2021.167350"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105240"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187433"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1187292"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.15.7131-7141.2001"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.07.008"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01112-20"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02321-10"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s007050050335"},{"key":"e_1_3_4_32_2","first-page":"397","article-title":"Contribution to the heat resistance of adenoviruses. Preliminary report","volume":"20","author":"Bartha A.","year":"1970","unstructured":"A. Bartha, J. Kisary, Contribution to the heat resistance of adenoviruses. Preliminary report. Acta Vet. Acad. Sci. Hung. 20, 397\u2013398 (1970).","journal-title":"Acta Vet. Acad. Sci. Hung."},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040385"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.537498"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade9910"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2009.202"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/5799"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.2786"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2010.05.003"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4193"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4169"},{"key":"e_1_3_4_42_2","volume-title":"UCSF Pyem v0.5","author":"Asarnow D.","year":"2019","unstructured":"D. Asarnow, E. Palovcak, Y. Cheng, UCSF Pyem v0.5 (Zenodo, 2019)."},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.05.004"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2011.11.010"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20084"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2006.05.009"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07487-w"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444904019158"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1107\/S2059798318006551"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-020-0914-9"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.3235"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2011.75"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku316"},{"key":"e_1_3_4_54_2","doi-asserted-by":"crossref","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 1. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9YD0\/pdb. Deposited 16 September 2025.","DOI":"10.2210\/pdb9yd0\/pdb"},{"key":"e_1_3_4_55_2","doi-asserted-by":"crossref","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 2. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9YCJ\/pdb. Deposited 17 September 2025.","DOI":"10.2210\/pdb9ycj\/pdb"},{"key":"e_1_3_4_56_2","doi-asserted-by":"crossref","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 3. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9YCI\/pdb. Deposited 17 September 2025.","DOI":"10.2210\/pdb9yci\/pdb"},{"key":"e_1_3_4_57_2","doi-asserted-by":"crossref","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 4. Protein Data Bank. https:\/\/doi.org\/10.2210\/pdb9YCH\/pdb. Deposited 18 September 2025.","DOI":"10.2210\/pdb9ych\/pdb"},{"key":"e_1_3_4_58_2","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP. Electron Microscopy Data Bank. https:\/\/www.ebi.ac.uk\/emdb\/EMD-72794. Deposited 18 September 2025."},{"key":"e_1_3_4_59_2","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 1. Electron Microscopy Data Bank. https:\/\/www.ebi.ac.uk\/emdb\/EMD-72793. Deposited 16 September 2025."},{"key":"e_1_3_4_60_2","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 2. Electron Microscopy Data Bank. https:\/\/www.ebi.ac.uk\/emdb\/EMD-72774. Deposited 17 September 2025."},{"key":"e_1_3_4_61_2","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 3. Electron Microscopy Data Bank. https:\/\/www.ebi.ac.uk\/emdb\/EMD-72773. Deposited 17 September 2025"},{"key":"e_1_3_4_62_2","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 VLP Class 4. Electron Microscopy Data Bank. https:\/\/www.ebi.ac.uk\/emdb\/EMD-72772. Deposited 18 September 2025."},{"key":"e_1_3_4_63_2","unstructured":"R. Khayat K. Madoo Structure of the Adenovirus-7 PB-Fiber. Electron Microscopy Data Bank. https:\/\/www.ebi.ac.uk\/emdb\/EMD-72771. Deposited 18 September 2025."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2526969123","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T16:18:22Z","timestamp":1781626702000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2526969123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,16]]},"references-count":63,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2026,6,23]]}},"alternative-id":["10.1073\/pnas.2526969123"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2526969123","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,16]]},"assertion":[{"value":"2025-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2526969123"}}