{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:47:13Z","timestamp":1785923233192,"version":"3.56.0"},"reference-count":98,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FAPERJ\u2014Carlos Chagas Filho Foundation","award":["SEI-260003\/013205\/2024"],"award-info":[{"award-number":["SEI-260003\/013205\/2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Hantaviruses, the etiological agents of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), represent a high-risk zoonotic threat with substantial global health impact. Currently, there is no FDA-approved vaccine. The viral surface glycoprotein (GP) is crucial for host cell entry and is regarded as a key target for vaccine development. However, its variability among hantavirus species limits the effectiveness of conventional vaccine strategies. Epitope-based vaccines offer a promising alternative by enabling the design of broadly protective constructs. In this study, we applied immunoinformatics approaches to design a universal multi-epitope vaccine candidate targeting both HFRS- and HPS-associated hantaviruses through a multi-layered workflow integrating B-cell and T-cell epitope prediction, antigenicity scoring, IFN-\u03b3 induction potential, conservation analysis, and population coverage assessment. Viral GPs from SEOV, PUUV, SNV, and ANDV were analyzed using algorithms for B-cell and T-cell epitope prediction. Predicted epitopes were assessed for allergenicity, toxicity, conservation, and population coverage. Two vaccine constructs incorporating \u03b2-defensin or 50S ribosomal protein L7\/L12 as adjuvants were assessed for physicochemical properties, structural stability and immunogenic potential. Molecular docking analyses provided exploratory ectodomain-compatibility screening, suggesting potential interactions with TLR4 that require future experimental confirmation. The in silico immune simulations suggested potential robust and long-lasting responses with memory cell persistence exceeding one year. Simulations also indicated balanced humoral and cellular responses, robust antibody production, and long-term memory formation suggestive of durable protective immunity. These findings support the rational design of broad-spectrum multi-epitope vaccines against genetically diverse hantaviruses, offering a rational framework for preclinical development of next-generation universal vaccines against hantavirus-associated diseases.<\/jats:p>","DOI":"10.3390\/ijms27157021","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:16:22Z","timestamp":1785921382000},"page":"7021","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Broad-Spectrum Multi-Epitope Design Targeting Conserved Hantavirus Glycoproteins (Gn\/Gc): Chimeric Antigen Engineering and Structural Mapping"],"prefix":"10.3390","volume":"27","author":[{"given":"Silvia da Silva","family":"Fontes","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Hantaviroses e Rickettsioses, Instituto Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1754-5870","authenticated-orcid":false,"given":"Fernando Paiva","family":"Conte","sequence":"additional","affiliation":[{"name":"Pilot Plant Implantation Project, Immunobiological Technology Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5039-0604","authenticated-orcid":false,"given":"Jorlan","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hantaviroses e Rickettsioses, Instituto Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elba Regina Sampaio de","family":"Lemos","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hantaviroses e Rickettsioses, Instituto Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5848-404X","authenticated-orcid":false,"given":"Josu\u00e9 da Costa","family":"Lima-Junior","sequence":"additional","affiliation":[{"name":"Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7552-6643","authenticated-orcid":false,"given":"Renata Carvalho de","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hantaviroses e Rickettsioses, Instituto Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9772-849X","authenticated-orcid":false,"given":"Rodrigo Nunes","family":"Rodrigues-da-Silva","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Hantaviroses e Rickettsioses, Instituto Oswaldo Cruz, Oswaldo Cruz Foundation, Rio de Janeiro 21040-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Brocato, R.L., and Hooper, J.W. 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