{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:13:32Z","timestamp":1792790012414,"version":"4.5.0"},"reference-count":63,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council","award":["NSTC 113-2314-B-020-001"],"award-info":[{"award-number":["NSTC 113-2314-B-020-001"]}]},{"name":"National Science and Technology Council","award":["NSTC 114-2314-B-020-001"],"award-info":[{"award-number":["NSTC 114-2314-B-020-001"]}]},{"name":"Ministry of Education (MOE) in Taiwan","id":[{"id":"https:\/\/ror.org\/03m01yf64","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung"},{"name":"Center for Metabolic Disorders and Obesity, Kaohsiung Medical University, Taiwan","id":[{"id":"https:\/\/ror.org\/03gk81f96","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Objective: The Baculovirus Expression Vector System (BEVS) is an established eukaryotic platform for high-yield recombinant protein production and is widely utilized for generating vaccine antigens, including recombinant classical swine fever virus E2 glycoprotein, African swine fever virus structural proteins (p72, p30, and p54), and porcine reproductive and respiratory syndrome virus envelope proteins GP5 and M. These antigens interact with macrophage-associated receptors, including CD163 and CD206, to modulate immune responses through macrophage polarization. However, whether baculovirus vector-derived components intrinsically influence macrophage polarization remains unclear, raising concerns regarding potential impacts on biological activity, vaccine efficacy, and downstream purification strategies. Methods: In this study, an M2-like tumor-associated macrophage (TAM) model capable of repolarizing toward an M1-like phenotype was established to distinguish the transcriptomic effects of the baculovirus vector control (VC) from those of the recombinant antigen (A1). Comparative RNA sequencing, Gene Set Enrichment Analysis (GSEA), functional enrichment analyses, and linear regression analysis were performed to evaluate vector- and antigen-associated transcriptional responses. Results: Comprehensive transcriptomic analysis showed that VC treatment induced only minimal transcriptomic alterations, with limited immune-related pathway enrichment and expression profiles that remained highly similar to those of untreated M2-like TAMs. Furthermore, linear regression analysis demonstrated negligible correlations between VC-induced and A1-induced transcriptional responses indicating that the limited changes associated with the vector backbone did not correspond to the receptor-mediated immune responses elicited by the recombinant antigen. In contrast, A1 stimulation induced distinct transcriptional reprogramming characterized by enrichment of pro-inflammatory and immune-activation pathways and a shift toward an M1-like macrophage phenotype. Conclusions: These findings suggest the negligible correspondence between VC- and A1-induced transcriptional profiles further supports the transcriptomic noises and signals of the baculovirus vector and inserted proteins, reinforcing its suitability as a platform for macrophage-targeted vaccine development while providing a basis for future optimization of downstream purification strategies.<\/jats:p>","DOI":"10.3390\/vaccines14090816","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T16:07:29Z","timestamp":1789574849000},"page":"816","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Silent Vehicle: Validating the Biological Signals and Noises of Baculovirus Vectors in Macrophage-Targeted Vaccines"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5465-7958","authenticated-orcid":false,"given":"Beginda","family":"Ridwan","sequence":"first","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Department of Animal Product Technology, Faculty of Animal Science, Brawijaya University, Malang 65145, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Farrah Putri","family":"Salmanida","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4150-266X","authenticated-orcid":false,"given":"Rika","family":"Wahyuningtyas","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Department School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2963-9038","authenticated-orcid":false,"given":"Yin-Siew","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"given":"Mei-Li","family":"Wu","sequence":"additional","affiliation":[{"name":"Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Department of Food Science, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"given":"Wen-Bin","family":"Chung","sequence":"additional","affiliation":[{"name":"Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"College of Veterinary Medicine, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"given":"Chia-Tsai","family":"Chang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, China Medical University, Taichung 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9383-831X","authenticated-orcid":false,"given":"Ko-Tung","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Research Centre for Animal Biologics, National Pingtung University of Science and Technology, Neipu 912, Pingtung, Taiwan"},{"name":"Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung 804, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S1471-4906(02)02302-5","article-title":"Macrophage polarization: Tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes","volume":"23","author":"Mantovani","year":"2002","journal-title":"Trends Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.immuni.2014.06.008","article-title":"Macrophage activation and polarization: Nomenclature and experimental guidelines","volume":"41","author":"Murray","year":"2014","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nrclinonc.2016.217","article-title":"Tumour-associated macrophages as treatment targets in oncology","volume":"14","author":"Mantovani","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-associated macrophages: From mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41571-022-00620-6","article-title":"Clinical relevance of tumour-associated macrophages","volume":"19","author":"Pittet","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virusres.2010.10.009","article-title":"Porcine reproductive and respiratory syndrome virus: An update on an emerging and re-emerging viral disease of swine","volume":"154","author":"Lunney","year":"2010","journal-title":"Virus Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.antiviral.2019.02.018","article-title":"African swine fever","volume":"165","author":"Dixon","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.tvjl.2017.12.025","article-title":"African swine fever: A re-emerging viral disease threatening the global pig industry","volume":"233","author":"Montoya","year":"2018","journal-title":"Vet. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1038\/nbt1095","article-title":"Baculovirus as versatile vectors for protein expression in insect and mammalian cells","volume":"23","author":"Kost","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1099\/vir.0.067108-0","article-title":"Thirty years of baculovirus-insect cell protein expression: From dark horse to mainstream technology","volume":"96","author":"Pijlman","year":"2015","journal-title":"J. Gen. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1002\/biot.201400438","article-title":"The baculovirus expression vector system: A commercial manufacturing platform for viral vaccines and gene therapy vectors","volume":"10","author":"Felberbaum","year":"2015","journal-title":"Biotechnol. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"9944","DOI":"10.1128\/JVI.73.12.9944-9951.1999","article-title":"Baculovirus stimulates antiviral effects in mammalian cells","volume":"73","author":"Gronowski","year":"1999","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1128\/JVI.79.5.2847-2858.2005","article-title":"Involvement of the Toll-like receptor 9 signaling pathway in the induction of innate immunity by baculovirus","volume":"79","author":"Abe","year":"2005","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ono, C., Okamoto, T., Abe, T., and Matsuura, Y. (2018). Baculovirus as a Tool for Gene Delivery and Gene Therapy. Viruses, 10.","DOI":"10.3390\/v10090510"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wahyuningtyas, R., Lai, Y.S., Wu, M.L., Chen, H.W., Chung, W.B., Chaung, H.C., and Chang, K.T. (2021). Recombinant Antigen of Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2) Promotes M1 Repolarization of Porcine Alveolar Macrophages and Th1 Type Response. Vaccines, 9.","DOI":"10.3390\/vaccines9091009"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.it.2019.02.003","article-title":"Targeting Tumor-Associated Macrophages in Cancer","volume":"40","author":"Pathria","year":"2019","journal-title":"Trends Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.1923","article-title":"Fast gapped-read alignment with Bowtie 2","volume":"9","author":"Langmead","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Li, B., and Dewey, C.N. (2011). RSEM: Accurate transcript quantification from RNA-Seq data with or without a reference genome. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-323"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tang, D., Chen, M., Huang, X., Zhang, G., Zeng, L., Zhang, G., Wu, S., and Wang, Y. (2023). SRplot: A free online platform for data visualization and graphing. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0294236"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1093\/bioinformatics\/btz931","article-title":"ShinyGO: A graphical gene-set enrichment tool for animals and plants","volume":"36","author":"Ge","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: Tool for the unification of biology. The Gene Ontology Consortium","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database (MSigDB) hallmark gene set collection","volume":"1","author":"Liberzon","year":"2015","journal-title":"Cell Syst."},{"key":"ref_27","unstructured":"Wahyuningtyas, R. (2023). The Application of Porcine Reproductive and Respiratory Syndrome Virus-2 (PRRSV-2) Recombinant Antigens on Vaccine and Cancer Drugs Development. [Ph.D. Thesis, National Pingtung University of Science and Technology]."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"17450","DOI":"10.1074\/jbc.M116.717868","article-title":"Identification of Caspase-6 as a New Regulator of Alternatively Activated Macrophages","volume":"291","author":"Yao","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, Mechanisms, and Significance of Macrophage Plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cell.2010.03.014","article-title":"Macrophage diversity enhances tumor progression and metastasis","volume":"141","author":"Qian","year":"2010","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41577-019-0127-6","article-title":"Macrophages as regulators of tumour immunity and immunotherapy","volume":"19","author":"DeNardo","year":"2019","journal-title":"Nat. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.ccell.2019.02.009","article-title":"Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets","volume":"35","author":"Cassetta","year":"2019","journal-title":"Cancer Cell"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhang, Q.W., Liu, L., Gong, C.Y., Shi, H.S., Zeng, Y.H., Wang, X.Z., Zhao, Y.W., and Wei, Y.Q. (2012). Prognostic significance of tumor-associated macrophages in solid tumor: A meta-analysis of the literature. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0050946"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.cell.2018.05.060","article-title":"Single-Cell Map of Diverse Immune Phenotypes in the Breast Tumor Microenvironment","volume":"174","author":"Azizi","year":"2018","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1126\/science.1252510","article-title":"The cellular and molecular origin of tumor-associated macrophages","volume":"344","author":"Franklin","year":"2014","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.immuni.2014.01.006","article-title":"Transcriptome-based network analysis reveals a spectrum model of human macrophage activation","volume":"40","author":"Xue","year":"2014","journal-title":"Immunity"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage Polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Orecchioni, M., Ghosheh, Y., Pramod, A.B., and Ley, K. (2019). Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01084"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Italiani, P., and Boraschi, D. (2014). From Monocytes to M1\/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00514"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1038\/ni.1937","article-title":"Macrophage plasticity and interaction with lymphocyte subsets: Cancer as a paradigm","volume":"11","author":"Biswas","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.1016\/j.immuni.2021.07.007","article-title":"Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease","volume":"54","author":"Mulder","year":"2021","journal-title":"Immunity"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.immuni.2019.03.009","article-title":"Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species","volume":"50","author":"Zilionis","year":"2019","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"eaau0964","DOI":"10.1126\/science.aau0964","article-title":"Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches","volume":"363","author":"Chakarov","year":"2019","journal-title":"Science"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1038\/nri3088","article-title":"Transcriptional regulation of macrophage polarization: Enabling diversity with identity","volume":"11","author":"Lawrence","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/ni.3306","article-title":"Molecular control of activation and priming in macrophages","volume":"17","author":"Glass","year":"2016","journal-title":"Nat. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.it.2012.11.001","article-title":"Epigenetic regulation of macrophage polarization and function","volume":"34","author":"Ivashkiv","year":"2013","journal-title":"Trends Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1038\/nri2634","article-title":"Transcriptional control of the inflammatory response","volume":"9","author":"Medzhitov","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1038\/ni.1863","article-title":"The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors","volume":"11","author":"Kawai","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/nri3446","article-title":"The history of Toll-like receptors\u2014Redefining innate immunity","volume":"13","author":"Golenbock","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1615\/CritRevEukarGeneExpr.v20.i2.10","article-title":"Tumor necrosis factor-\u03b1 signaling in macrophages","volume":"20","author":"Parameswaran","year":"2010","journal-title":"Crit. Rev. Eukaryot. Gene Expr."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nri2586","article-title":"Structure and signalling in the IL-17 receptor family","volume":"9","author":"Gaffen","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease","volume":"1843","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1182\/blood-2010-07-273417","article-title":"Interleukin-1 in the pathogenesis and treatment of inflammatory diseases","volume":"117","author":"Dinarello","year":"2011","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1038\/nri2873","article-title":"Sterile inflammation: Sensing and reacting to damage","volume":"10","author":"Chen","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/s41577-018-0029-z","article-title":"IFN\u03b3: Signalling, epigenetics and roles in immunity, metabolism, disease and cancer immunotherapy","volume":"18","author":"Ivashkiv","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/S0092-8674(02)00971-6","article-title":"Integrins: Bidirectional, allosteric signaling machines","volume":"110","author":"Hynes","year":"2002","journal-title":"Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/0092-8674(94)90337-9","article-title":"Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm","volume":"76","author":"Springer","year":"1994","journal-title":"Cell"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"iii70","DOI":"10.1136\/ard.2008.098459","article-title":"The PI3K\/Akt\/mTOR pathway in innate immune cells: Emerging therapeutic applications","volume":"67","author":"Weichhart","year":"2008","journal-title":"Ann. Rheum. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nri2156","article-title":"Getting to the site of inflammation: The leukocyte adhesion cascade updated","volume":"7","author":"Ley","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"10099","DOI":"10.1073\/pnas.92.22.10099","article-title":"Efficient gene transfer into human hepatocytes by baculovirus vectors","volume":"92","author":"Hofmann","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Geeraerts, X., Bolli, E., Fendt, S.M., and Van Ginderachter, J.A. (2017). Macrophage Metabolism As Therapeutic Target for Cancer, Atherosclerosis, and Obesity. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.00289"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/816\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:30:32Z","timestamp":1789705832000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/816"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":63,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["vaccines14090816"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14090816","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]}}}