{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:59:05Z","timestamp":1785430745688,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000865","name":"Flu Lab","doi-asserted-by":"publisher","award":["OPP1214161"],"award-info":[{"award-number":["OPP1214161"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"award":["OPP1214161"],"award-info":[{"award-number":["OPP1214161"]}],"id":[{"id":"https:\/\/ror.org\/027hgk366","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Background: The elicitation of broadly neutralizing antibodies against conserved antigenic epitopes has been a focus of universal vaccine research. To facilitate immunofocusing on the conserved influenza hemagglutinin (HA) stalk, we designed headless trimeric antigens, initially focusing on subtypes H1, H3, and H5, and subsequently expanding to eight additional HA subtypes. Results: The designs were first evaluated in silico; they were predicted to fold correctly by AlphaFold2, and remained stable in molecular dynamics simulations in isolation, as well as bound to a broadly neutralizing antibody. The antigens expressed in HEK293-derived cells in high yields, and eluted predominantly as trimers in SEC-HPLC. Future work will explore the use of mosaic nanoparticles decorated with headless antigens of various subtypes for the optimal elicitation of broadly neutralizing anti-influenza antibodies. Overall, our study advances the use of headless HA trimers as modular antigens toward a universal influenza vaccine.<\/jats:p>","DOI":"10.3390\/antib15040064","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:47:41Z","timestamp":1785145661000},"page":"64","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational Design and Expression of Headless Influenza Hemagglutinin Antigens Toward a Modular Universal Nanoparticle Vaccine"],"prefix":"10.3390","volume":"15","author":[{"given":"Victor","family":"Ovchinnikov","sequence":"first","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Karplus","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA"},{"name":"Laboratoire de Chimie Biophysique, Institut de Science et d\u2019Ing\u00e9nierie Supramol\u00e9culaires, Universit\u00e9 de Strasbourg, 67000 Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S2213-2600(18)30496-X","article-title":"Mortality, Morbidity, and Hospitalisations Due to Influenza Lower Respiratory Tract Infections, 2017: An Analysis for the Global Burden of Disease Study 2017","volume":"7","author":"Troeger","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/infdis\/jiy103","article-title":"A Universal Influenza Vaccine: The Strategic Plan for the National Institute of Allergy and Infectious Diseases","volume":"218","author":"Erbelding","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1128\/JVI.80.7.3675-3678.2006","article-title":"Comparison of the Mutation Rates of Human Influenza a and B Viruses","volume":"80","author":"Nobusawa","year":"2006","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1016\/j.cell.2019.03.048","article-title":"Antibodies to a Conserved Influenza Head Interface Epitope Protect by an IgG Subtype-Dependent Mechanism","volume":"177","author":"Watanabe","year":"2019","journal-title":"Cell"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/ni.3684","article-title":"Defining the Antibody Cross-Reactome Directed Against the Influenza Virus Surface Glycoproteins","volume":"18","author":"Nachbagauer","year":"2017","journal-title":"Nat. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.coviro.2017.03.002","article-title":"Tackling Influenza with Broadly Neutralizing Antibodies","volume":"24","author":"Corti","year":"2017","journal-title":"Curr. Opin. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"E2514","DOI":"10.1073\/pnas.1402766111","article-title":"Influenza Hemagglutinin Stem-Fragment Immunogen Elicits Broadly Neutralizing Antibodies and Confers Heterologous Protection","volume":"111","author":"Mallajosyula","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13133","DOI":"10.1073\/pnas.1414070111","article-title":"Induction of Broadly Cross-Reactive Antibody Responses to the Influenza Ha Stem Region Following H5N1 Vaccination in Humans","volume":"111","author":"Ellebedy","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.cell.2016.06.043","article-title":"Vaccine-Induced Antibodies That Neutralize Group 1 and Group 2 Influenza a Viruses","volume":"166","author":"Joyce","year":"2016","journal-title":"Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.coviro.2021.09.015","article-title":"Strategies for Eliciting Multiple Lineages of Broadly Neutralizing Antibodies to HIV by Vaccination","volume":"51","author":"Mu","year":"2021","journal-title":"Curr. Opin. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/j.cell.2016.05.073","article-title":"Structure and Function Analysis of an Antibody Recognizing All Influenza a Subtypes","volume":"166","author":"Kallewaard","year":"2016","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1126\/science.1205669","article-title":"A Neutralizing Antibody Selected from Plasma Cells That Binds to Group 1 and Group 2 Influenza a Hemagglutinins","volume":"333","author":"Corti","year":"2011","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9047","DOI":"10.1073\/pnas.1118979109","article-title":"Pandemic H1N1 Influenza Vaccine Induces a Recall Response in Humans That Favors Broadly Cross-Reactive Memory B Cells","volume":"109","author":"Li","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e01996-15","DOI":"10.1128\/mBio.01996-15","article-title":"Age Dependence and Isotype Specificity of Influenza Virus Hemagglutinin Stalk-Reactive Antibodies in Humans","volume":"7","author":"Nachbagauer","year":"2016","journal-title":"mBio"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3492","DOI":"10.1038\/s41598-019-40175-8","article-title":"Autoreactivity Profiles of Influenza Hemagglutinin Broadly Neutralizing antibodies","volume":"9","author":"Bajic","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"316ra192","DOI":"10.1126\/scitranslmed.aad0522","article-title":"Immune History Profoundly Affects Broadly Protective B Cell Responses to Influenza","volume":"7","author":"Andrews","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1016\/j.chom.2019.04.003","article-title":"Influenza Antigen Engineering Focuses Immune Responses to a Subdominant but Broadly Protective Viral Epitope","volume":"25","author":"Bajic","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"17221","DOI":"10.1073\/pnas.1920321117","article-title":"Original Antigenic Sin Priming of Influenza Virus Hemagglutinin Stalk Antibodies","volume":"117","author":"Arevalo","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.cels.2020.09.005","article-title":"Defining and Manipulating B Cell Immunodominance Hierarchies to Elicit Broadly Neutralizing Antibody Responses Against Influenza Virus","volume":"11","author":"Amitai","year":"2020","journal-title":"Cell Syst."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"850","DOI":"10.1172\/JCI123366","article-title":"Subdominance and Poor Intrinsic Immunogenicity Limit Humoral Immunity Targeting Influenza Ha Stem","volume":"129","author":"Tan","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, S. (2017). Optimal Sequential Immunization Can Focus Antibody Responses Against Diversity Loss and Distraction. PLoS Comput. Biol., 13.","DOI":"10.1371\/journal.pcbi.1005336"},{"key":"ref_22","unstructured":"Ives, S., B\u00fcrckert, J.P., Pettus, C., Pe\u00f1ate, K., Hovde, R., Bayless, N., Shanghavi, D., Glanville, K., Calgua, E., and Youssef, S. (Res. Sq., 2021). A General Solution to Broad-Spectrum Vaccine Design for Rapidly Mutating Viruses, Res. Sq., submitted."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4720","DOI":"10.1128\/JVI.03152-15","article-title":"Design and Characterization of a Computationally Optimized Broadly Reactive Hemagglutinin Vaccine for H1N1 Influenza Viruses","volume":"90","author":"Carter","year":"2016","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"E7039","DOI":"10.1073\/pnas.1614940113","article-title":"Optimal Immunization Cocktails Can Promote Induction of Broadly Neutralizing Abs Against Highly Mutable Pathogens","volume":"113","author":"Shaffer","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41590-018-0305-x","article-title":"Mosaic Nanoparticle Display of Diverse Influenza Virus Hemagglutinins Elicits Broad B Cell Responses","volume":"20","author":"Kanekiyo","year":"2019","journal-title":"Nat. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1038\/s41467-020-14579-4","article-title":"Glycan Repositioning of Influenza Hemagglutinin Stem Facilitates the Elicitation of Protective Cross-Group Antibody Responses","volume":"11","author":"Hutchinson","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cohen, A., Yang, Z., Gnanapragasam, P., Ou, S., Dam, K., Wang, H., and Bjorkman, P. (2021). Construction, Characterization, and Immunization of Nanoparticles That Display a Diverse Array of Influenza Ha Trimers. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0247963"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1126\/science.abf6840","article-title":"Mosaic Nanoparticles Elicit Cross-Reactive Immune Responses to Zoonotic Coronaviruses in Mice","volume":"371","author":"Cohen","year":"2021","journal-title":"Science"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e02810-18","DOI":"10.1128\/mBio.02810-18","article-title":"Design of Nanoparticulate Group 2 Influenza Virus Hemagglutinin Stem Antigens That Activate Unmutated Ancestor B Cell Receptors of Broadly Neutralizing Antibody Lineages","volume":"10","author":"Corbett","year":"2019","journal-title":"mBio"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e01166-24","DOI":"10.1128\/jvi.01166-24","article-title":"Headless Hemagglutinin-Containing Influenza Viral Particles Direct Immune Responses Toward More Conserved Epitopes","volume":"98","author":"Hamele","year":"2024","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ovchinnikov, V., and Karplus, M. (2022). A Coarse-Grained Model of Affinity Maturation Indicates the Importance of B-Cell Receptor Avidity in Epitope Subdominance. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.816634"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e00018-10","DOI":"10.1128\/mBio.00018-10","article-title":"Influenza Virus Vaccine Based on the Conserved Hemagglutinin Stalk Domain","volume":"1","author":"Steel","year":"2010","journal-title":"mBio"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1073\/pnas.1308701110","article-title":"Production and Stabilization of the Trimeric Influenza Hemagglutinin Stem Domain for Potentially Broadly Protective Influenza Vaccines","volume":"111","author":"Lu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1126\/science.aac7263","article-title":"A Stable Trimeric Influenza Hemagglutinin Stem As a Broadly Protective Immunogen","volume":"349","author":"Impagliazzo","year":"2015","journal-title":"Science"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1038\/nm.3927","article-title":"Hemagglutinin-Stem Nanoparticles Generate Heterosubtypic Influenza Protection","volume":"21","author":"Yassine","year":"2015","journal-title":"Nat. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22666","DOI":"10.1038\/srep22666","article-title":"Stalking Influenza by Vaccination with Pre-Fusion Headless Ha Mini-Stem","volume":"6","author":"Valkenburg","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2405","DOI":"10.1016\/j.immuni.2022.10.015","article-title":"Co-Immunization with Hemagglutinin Stem Immunogens Elicits Cross-Group Neutralizing Antibodies and Broad Protection Against Influenza a Viruses","volume":"55","author":"Moin","year":"2022","journal-title":"Immunity"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jmb.2013.10.021","article-title":"Structural Analysis and Optimization of the Covalent Association Between SpyCatcher and a Peptide Tag","volume":"426","author":"Li","year":"2014","journal-title":"J. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/nature18010","article-title":"Design of a Hyperstable 60-Subunit Protein Dodecahedron","volume":"535","author":"Hsia","year":"2016","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.biocel.2011.09.009","article-title":"The Crucial Role of Trimerization Domains in Collagen Folding","volume":"44","author":"Boudko","year":"2012","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1016\/j.jmb.2004.02.020","article-title":"Very Fast Folding and Association of a Trimerization Domain from Bacteriophage T4 Fibritin","volume":"337","author":"Kapinos","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/j.jmb.2009.07.057","article-title":"Crystal Structure of Human Collagen XVIII Trimerization Domain: A Novel Collagen Trimerization Fold","volume":"392","author":"Boudko","year":"2009","journal-title":"J. Mol. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.matbio.2010.09.005","article-title":"Crystal Structure of the Human Collagen XV Trimerization Domain: A Potent Trimerizing Unit Common to Multiplexin Collagens","volume":"30","author":"Wirz","year":"2011","journal-title":"Matrix Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9976","DOI":"10.1021\/acs.jpcb.4c04100","article-title":"CHARMM at 45: Enhancements in Accessibility, Functionality, and Speed","volume":"128","author":"Hwang","year":"2024","journal-title":"J. Phys. Chem. B"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1711","DOI":"10.1002\/prot.26257","article-title":"Applying and Improving AlphaFold at CASP14","volume":"89","author":"Jumper","year":"2021","journal-title":"Proteins"},{"key":"ref_46","unstructured":"(MATLAB, 2010). MATLAB, version 7.10.0 (R2010a)."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1866","DOI":"10.1021\/acs.jctc.9b01072","article-title":"Microsecond Molecular Dynamics Simulations of Proteins Using a Quasi-Equilibrium Solvation Shell Model","volume":"16","author":"Ovchinnikov","year":"2020","journal-title":"J. Chem. Theor. Comput."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1002\/jcc.21209","article-title":"Accelerating Molecular Dynamic Simulation on Graphics Processing Units","volume":"30","author":"Friedrichs","year":"2009","journal-title":"J. Comput. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8565","DOI":"10.1021\/acs.jpcb.3c05236","article-title":"Free Energy Simulations of Receptor-Binding Domain Opening in the SARS-CoV-2 Spike Indicate a Barrierless Transition with Slow Conformational Motions","volume":"127","author":"Ovchinnikov","year":"2023","journal-title":"J. Phys. Chem. B"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1038\/nmeth.4067","article-title":"CHARMM36m: An Improved Force Field for Folded and Intrinsically Disordered Proteins","volume":"14","author":"Huang","year":"2017","journal-title":"Nat. Methods"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6665","DOI":"10.1073\/pnas.0408037102","article-title":"Potential Energy Functions for Atomic-Level Simulations of Water and Organic and Biomolecular Systems","volume":"102","author":"Jorgensen","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"5451","DOI":"10.1063\/1.469273","article-title":"A Generalized Reaction Field Method for Molecular Dynamics Simulations","volume":"102","author":"Tironi","year":"1995","journal-title":"J. Chem. Phys."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0263-7855(96)00018-5","article-title":"VMD: Visual Molecular Dynamics","volume":"14","author":"Humphrey","year":"1996","journal-title":"J. Mol. Graph."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6395","DOI":"10.1073\/pnas.0408677102","article-title":"Solving the Protein Sequence Metric Problem","volume":"102","author":"Atchley","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Ovchinnikov, V., and Karplus, M. (2025). Phenomenological Modeling of Antibody Response from Vaccine Strain Composition. Antibodies, 14.","DOI":"10.3390\/antib14010006"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1128\/JVI.02005-07","article-title":"The Influenza Virus Resource at the National Center for Biotechnology Information","volume":"82","author":"Bao","year":"2008","journal-title":"J. Virol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/S0092-8674(00)81771-7","article-title":"Structure of the Hemagglutinin Precursor Cleavage Site, a Determinant of Influenza Pathogenicity and the Origin of the Labile Conformation","volume":"95","author":"Chen","year":"1998","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.tips.2009.11.001","article-title":"Immunological Mechanism Underlying the Immune Response to Recombinant Human Protein Therapeutics","volume":"31","author":"Sauerborn","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1111\/j.1742-4658.2009.07065.x","article-title":"Polysaccharide Binding Sites in Hyaluronate Lyase\u2013Crystal Structures of Native Phage-Encoded Hyaluronate Lyase and Its Complexes with Ascorbic Acid and Lactose","volume":"276","author":"Mishra","year":"2009","journal-title":"FEBS J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41541-017-0026-4","article-title":"A Universal Influenza Virus Vaccine Candidate Confers Protection Against Pandemic H1N1 Infection in Preclinical Ferret Studies","volume":"2","author":"Nachbagauer","year":"2017","journal-title":"npj Vaccines"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/molbev\/mst010","article-title":"MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability","volume":"30","author":"Katoh","year":"2013","journal-title":"Mol. Biol. Evol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1126\/science.abm0271","article-title":"A Multivalent Nucleoside-Modified MRNa Vaccine Against All Known Influenza Virus Subtypes","volume":"378","author":"Arevalo","year":"2022","journal-title":"Science"}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/4\/64\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T04:28:35Z","timestamp":1785299315000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/15\/4\/64"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,27]]},"references-count":62,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antib15040064"],"URL":"https:\/\/doi.org\/10.3390\/antib15040064","relation":{},"ISSN":["2073-4468"],"issn-type":[{"value":"2073-4468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,27]]}}}