{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:36:38Z","timestamp":1792722998066,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T00:00:00Z","timestamp":1770422400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002467","name":"Dankook University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002467","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Spatial transcriptomics (ST) enables genome-wide gene expression profiling while preserving tissue architecture, bridging the gap between bulk, single-cell, and histological analyses. Originating in 2016 and rapidly evolving since, ST has transformed infectious disease research by mapping host\u2013pathogen interactions directly within intact tissues. Current platforms fall into two categories: sequencing-based methods (Visium, GeoMx, Stereo-seq) offering whole-transcriptome coverage at modest resolution and imaging-based platforms (Xenium, CosMx, MERFISH) providing single-cell or subcellular detail with targeted gene panels. These technologies reveal spatially organized immune responses, local tissue remodeling, and pathogen niches across viruses, bacteria, and parasites. In viral infection, ST uncovered heterogeneity in COVID-19 lung microenvironments, spatial immune activation in lymphoid tissues, and variant-specific inflammatory patterns. In bacterial disease, ST delineated granuloma architecture in tuberculosis and mapped vaccine-induced lung responses in Shigella studies. Parasitic infection studies identified localized inflammatory hotspots and microenvironmental control of T-cell differentiation in malaria. Despite powerful insights, ST faces constraints including RNA quality limitations, tradeoffs between resolution and transcript breadth, high cost, and analytical complexity. Nonetheless, ST increasingly informs vaccine design by identifying tissue-specific immune programs and protective microenvironments and is poised to become a standard tool for infectious disease biology.<\/jats:p>","DOI":"10.3390\/vaccines14020158","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T08:15:54Z","timestamp":1770624954000},"page":"158","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Advances in Spatial Transcriptomics for Infectious Disease Research: Insight for Vaccine Development"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-5573","authenticated-orcid":false,"given":"Taehwan","family":"Oh","sequence":"first","affiliation":[{"name":"Department of Microbiology, College of Medicine, Dankook University, Cheonan 31116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1126\/science.aaf2403","article-title":"Visualization and analysis of gene expression in tissue sections by spatial transcriptomics","volume":"353","author":"Vickovic","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1468","DOI":"10.1111\/febs.14435","article-title":"Placing RNA in context and space\u2014Methods for spatially resolved transcriptomics","volume":"286","author":"Strell","year":"2019","journal-title":"FEBS J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41592-020-01033-y","article-title":"Method of the Year: Spatially resolved transcriptomics","volume":"18","author":"Marx","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_4","first-page":"38","article-title":"Spatial transcriptomics: Recent developments and insights in respiratory research","volume":"10","author":"Wang","year":"2023","journal-title":"Mil. Med. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/s41368-021-00146-0","article-title":"From bulk, single-cell to spatial RNA sequencing","volume":"13","author":"Li","year":"2021","journal-title":"Int. J. Oral. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nmeth.1315","article-title":"mRNA-Seq whole-transcriptome analysis of a single cell","volume":"6","author":"Tang","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_7","first-page":"45","article-title":"Advances in single-cell sequencing: Insights from organ transplantation","volume":"8","author":"Wang","year":"2021","journal-title":"Mil. Med. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e157837","DOI":"10.1172\/jci.insight.157837","article-title":"Spatial transcriptomic characterization of COVID-19 pneumonitis identifies immune circuits related to tissue injury","volume":"8","author":"Cross","year":"2023","journal-title":"JCI Insight"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6319","DOI":"10.1038\/s41467-020-20139-7","article-title":"Temporal and spatial heterogeneity of host response to SARS-CoV-2 pulmonary infection","volume":"11","author":"Desai","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1038\/s41577-025-01210-0","article-title":"Spatial immunometabolic zonation in tuberculosis granulomas","volume":"25","author":"Sinha","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1101\/gr.275224.121","article-title":"Advances in spatial transcriptomic data analysis","volume":"31","author":"Dries","year":"2021","journal-title":"Genome Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12967-023-04150-2","article-title":"Advances in spatial transcriptomics and related data analysis strategies","volume":"21","author":"Du","year":"2023","journal-title":"J. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41586-021-03570-8","article-title":"COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets","volume":"595","author":"Delorey","year":"2021","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"eabo5070","DOI":"10.1126\/scitranslmed.abo5070","article-title":"SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice","volume":"14","author":"Dinnon","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1038\/s42003-023-05253-8","article-title":"Spatial transcriptome atlas reveals pulmonary microstructure-specific COVID-19 gene signatures in cynomolgus macaques","volume":"6","author":"Oh","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e28847","DOI":"10.1002\/jmv.28847","article-title":"Comparative spatial transcriptomic profiling of severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants infections in the lungs of cynomolgus macaques","volume":"95","author":"Oh","year":"2023","journal-title":"J. Med. Virol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"102180","DOI":"10.1016\/j.labinv.2024.102180","article-title":"Spatiotemporal Cellular Dynamics of Germinal Center Reaction in Coronavirus Disease 2019 Lung-Draining Lymph Node Based on Imaging-Based Spatial Transcriptomics","volume":"105","author":"Oh","year":"2025","journal-title":"Lab. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110589","DOI":"10.1016\/j.clim.2025.110589","article-title":"Structural and functional characteristics of local immune memory formation in SARS-CoV-2-infected cynomolgus macaques","volume":"281","author":"Oh","year":"2025","journal-title":"Clin. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"5814","DOI":"10.1038\/s41467-023-41387-3","article-title":"Epithelial plasticity and innate immune activation promote lung tissue remodeling following respiratory viral infection","volume":"14","author":"Beppu","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"100242","DOI":"10.1016\/j.xcrm.2021.100242","article-title":"Spatial mapping of sars-cov-2 and h1n1 lung injury identifies differential transcriptional signatures","volume":"2","author":"Margaroli","year":"2021","journal-title":"Cell Rep. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6597","DOI":"10.1038\/s41467-023-42021-y","article-title":"A spatial sequencing atlas of age-induced changes in the lung during influenza infection","volume":"14","author":"Kasmani","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1136\/gutjnl-2023-330577","article-title":"Spatial transcriptomics reveals a low extent of transcriptionally active hepatitis B virus integration in patients with HBsAg loss","volume":"73","author":"Yu","year":"2024","journal-title":"Gut"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e100067","DOI":"10.1136\/egastro-2024-100067","article-title":"Characterisation of HBV and co-infection with HDV and HIV through spatial transcriptomics","volume":"2","author":"Cross","year":"2024","journal-title":"EGastroenterology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e01909-24","DOI":"10.1128\/mbio.01909-24","article-title":"Spatial technologies to evaluate the HIV-1 reservoir and its microenvironment in the lymph node","volume":"15","author":"Zaman","year":"2024","journal-title":"Mbio"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Boger, M.F., Kaldhusdal, V., Pascual-Reguant, A., Kroh, S., Uecker, R., Burgener, A.D., Lajoie, J., Omollo, K., Kimani, J., and Fowke, K.R. (2024). Spatial transcriptomics and in situ immune cell profiling of the host ectocervical landscape of HIV infected Kenyan sex working women. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1483346"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"McCaffrey, E.F., Delmastro, A.C., Fitzhugh, I., Ranek, J.S., Douglas, S., Peters, J.M., Fullaway, C.C., Bosse, M., Liu, C.C., and Gillen, C. (2025). The immunometabolic topography of tuberculosis granulomas governs cellular organization and bacterial control. bioRxiv.","DOI":"10.1101\/2025.02.18.638923"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e01559-25","DOI":"10.1128\/mbio.01559-25","article-title":"Paired single-cell and spatial transcriptional profiling reveals a central osteopontin macrophage response mediating tuberculous granuloma formation","volume":"16","author":"Pyle","year":"2025","journal-title":"mBio"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Adduri, S., Bohorquez, J.A., Adejare, O., Rincon, D., Tucker, T., Konduru, N.V., and Yi, G. (2025). Spatial transcriptomic analysis of HIV and tuberculosis coinfection in a humanized mouse model reveals specific transcription patterns, immune responses and early morphological alteration signaling. bioRxiv.","DOI":"10.1101\/2025.01.29.635571"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Lu, T., Kramer, S.T., York, M.A., Zahan, M.N., Howlader, D.R., Dietz, Z.K., Whittier, S.K., Bivens, N.J., Jurkevich, A., and Coghill, L.M. (2025). Spatial visualization provides insight into immune modulation by an L-DBF vaccine formulation against Shigella. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1577040"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7105","DOI":"10.1038\/s41467-024-51418-2","article-title":"Host-pathogen interactions in the Plasmodium-infected mouse liver at spatial and single-cell resolution","volume":"15","author":"Hildebrandt","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114317","DOI":"10.1016\/j.celrep.2024.114317","article-title":"Plasmodium infection induces phenotypic, clonal, and spatial diversity among differentiating CD4+ T cells","volume":"43","author":"Williams","year":"2024","journal-title":"Cell Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1093\/jmcb\/mjaa028","article-title":"Transcriptional output, cell-type densities, and normalization in spatial transcriptomics","volume":"12","author":"Saiselet","year":"2020","journal-title":"J. Mol. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jtho.2019.12.112","article-title":"Three-dimensional histologic, immunohistochemical, and multiplex immunofluorescence analyses of dynamic vessel co-option of spread through air spaces in lung adenocarcinoma","volume":"15","author":"Yagi","year":"2020","journal-title":"J. Thorac. Oncol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.tibtech.2020.05.006","article-title":"Uncovering an organ\u2019s molecular architecture at single-cell resolution by spatially resolved transcriptomics","volume":"39","author":"Liao","year":"2021","journal-title":"Trends Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41577-023-00853-1","article-title":"Assessing the generation of tissue resident memory T cells by vaccines","volume":"23","author":"Rotrosen","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"ofab483","DOI":"10.1093\/ofid\/ofab483","article-title":"Harnessing the potential of multiomics studies for precision medicine in infectious disease","volume":"Volume 8","author":"Ward","year":"2021","journal-title":"Open Forum Infectious Diseases"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1021\/acsinfecdis.9b00080","article-title":"Multi-omics strategies uncover host\u2013pathogen interactions","volume":"5","author":"Khan","year":"2019","journal-title":"ACS Infect. Dis."},{"key":"ref_38","first-page":"100061","article-title":"Revolutionizing infectious disease surveillance: Multi-omics technologies and AI-driven integration","volume":"3","author":"Aswini","year":"2025","journal-title":"Decod. Infect. Transm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s12985-025-02640-x","article-title":"Advances in bioinformatics and multi-omics integration: Transforming viral infectious disease research in veterinary medicine","volume":"22","author":"Elrashedy","year":"2025","journal-title":"Virol. J."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/2\/158\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T05:22:07Z","timestamp":1770700927000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/2\/158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,7]]},"references-count":39,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["vaccines14020158"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14020158","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,7]]}}}