{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T11:09:35Z","timestamp":1772449775343,"version":"3.50.1"},"reference-count":68,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018688","name":"Korea National Institute of Health","doi-asserted-by":"publisher","award":["2022-NI070-02"],"award-info":[{"award-number":["2022-NI070-02"]}],"id":[{"id":"10.13039\/100018688","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Tuberculosis (TB) remains a major global health challenge, and the Bacillus Calmette\u2013Gu\u00e9rin (BCG) vaccine has limited efficacy against adult pulmonary disease. Protein subunit vaccines are a promising alternative but require strong adjuvants to induce cell-mediated immunity. Synthetic agonists targeting toll-like receptor 4 (TLR4) and stimulators of interferon genes (STINGs) have emerged as effective immunostimulants. Therefore, we aimed to evaluate the immunogenicity and protective efficacy of Ag85B-based subunit vaccines formulated with synthetic TLR4 and STING agonists in a BCG-boosted mouse model. Methods: Three synthetic adjuvants\u2014QTP709-1, QTP709-3, and QTP701\u2014were formulated as oil-in-water emulsions containing distinct surfactant and immunostimulant components. The potential of vaccine formulations to activate dendritic cells (DCs) and elicit Ag85B-specific immune responses, including IgG subclass levels, interferon-\u03b3 (IFN-\u03b3) enzyme-linked immunosorbent spots, and polyfunctional T-cell responses, was assessed by flow cytometry. Protective efficacy was evaluated based on pulmonary bacterial burden and histopathology following Mycobacterium tuberculosis (M. tb) Erdman challenge. Results: All formulations promoted DC maturation and enhanced antigen-specific immune responses. Each adjuvant elicited strong Ag85B-specific humoral immunity, increased IFN-\u03b3 secretion, and polyfunctional CD4+ and CD8+ T cells co-producing IFN-\u03b3, TNF-\u03b1, and interleukin-2. Among them, QTP709-1 was associated with increased levels of chemokine receptor 5-associated chemokines and showed a trend toward reduced lung bacterial burden and histopathological inflammation following M. tb challenge. Conclusions: Synthetic TLR4 and STING agonists were associated with enhanced immunogenicity of TB subunit vaccines and showed evidence of protective potential, with TLR4-based formulations exhibiting more pronounced immunological responses. QTP709-1 exhibited strong immunostimulatory and protective effects, supporting its potential as a candidate adjuvant for next-generation TB vaccines.<\/jats:p>","DOI":"10.3390\/vaccines14030214","type":"journal-article","created":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T08:31:19Z","timestamp":1772181079000},"page":"214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunogenicity and Protective Effects of an Ag85B Tuberculosis Subunit Vaccine Formulated with Synthetic TLR4 Agonists in BCG-Boosted Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Soo-Min","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, 212 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"},{"name":"College of Pharmacy, Korea University, Sejong 30019, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6777-9614","authenticated-orcid":false,"given":"Jin-Seung","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, 212 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"EunJung","family":"Shin","sequence":"additional","affiliation":[{"name":"Bio Research Center, Quratis Inc., Osong 28161, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhee","family":"Lee","sequence":"additional","affiliation":[{"name":"Bio Research Center, Quratis Inc., Osong 28161, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"You-Jin","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, 212 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9819-2398","authenticated-orcid":false,"given":"Hye-Sook","family":"Jeong","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, 212 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5599-0553","authenticated-orcid":false,"given":"Yong Woo","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Korea University, Sejong 30019, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dokeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, 212 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","first-page":"107325","article-title":"Insights from the 2024 WHO Global Tuberculosis Report\u2014More Comprehensive Action, Innovation, and Investments required for achieving WHO End TB goals","volume":"150","author":"Goletti","year":"2025","journal-title":"Int. J. Infect. Dis. IJID Off. Publ. Int. Soc. Infect. Dis."},{"key":"ref_2","first-page":"E9","article-title":"The history of tuberculosis: From the first historical records to the isolation of Koch\u2019s bacillus","volume":"58","author":"Barberis","year":"2017","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Xie, S., Xiao, H., Xu, L., Zhang, F., and Luo, M. (2025). Decadal trends and regional disparities in tuberculosis burden: A comprehensive analysis of global, African, and Southeast Asian data from the GBD 1990\u20132021. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1467509"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e012466","DOI":"10.1136\/bmjgh-2023-012466","article-title":"The potential impact of novel tuberculosis vaccines on health equity and financial protection in low-income and middle-income countries","volume":"8","author":"Portnoy","year":"2023","journal-title":"BMJ Glob. Health"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e2","DOI":"10.1016\/S1473-3099(21)00403-5","article-title":"100 years of Mycobacterium bovis bacille Calmette-Gu\u00e9rin","volume":"22","author":"Lange","year":"2022","journal-title":"Lancet. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41467-023-44252-5","article-title":"BCG vaccination-induced acquired control of mycobacterial growth differs from growth control preexisting to BCG vaccination","volume":"15","author":"Li","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s43556-024-00243-6","article-title":"Tuberculosis vaccines and therapeutic drug: Challenges and future directions","volume":"6","author":"An","year":"2025","journal-title":"Mol. Biomed."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/s41541-023-00750-7","article-title":"Key advances in vaccine development for tuberculosis-success and challenges","volume":"8","author":"Lai","year":"2023","journal-title":"npj Vaccines"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"101431","DOI":"10.1016\/j.smim.2020.101431","article-title":"Key recent advances in TB vaccine development and understanding of protective immune responses against Mycobacterium tuberculosis","volume":"50","author":"Scriba","year":"2020","journal-title":"Semin. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Agrawal, N., Ates, L.S., Schille, S., Chaturvedi, A., Vogt, J., Vukovic, N., Vogel, A.B., Diekmann, J., Diken, M., and \u015eahin, U. (2025). mRNA-based tuberculosis vaccines BNT164a1 and BNT164b1 are immunogenic, well-tolerated and efficacious in rodent models. bioRxiv.","DOI":"10.1101\/2025.09.30.679428"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Kazakova, A., Zhelnov, P., Sidorov, R., Rogova, A., Vasileva, O., Ivanov, R., Reshetnikov, V., and Muslimov, A. (2024). DNA and RNA vaccines against tuberculosis: A scoping review of human and animal studies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1457327"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/s41392-024-02002-z","article-title":"Progress and prospects of mRNA-based drugs in pre-clinical and clinical applications","volume":"9","author":"Shi","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1016\/j.drudis.2020.09.005","article-title":"Recent progress in the design of DNA vaccines against tuberculosis","volume":"25","author":"Jahangiri","year":"2020","journal-title":"Drug Discov. Today"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Xu, J.C., Hu, Z.D., and Fan, X.Y. (2023). Advances in protein subunit vaccines against tuberculosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1238586"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kozak, M., and Hu, J. (2023). The Integrated Consideration of Vaccine Platforms, Adjuvants, and Delivery Routes for Successful Vaccine Development. Vaccines, 11.","DOI":"10.3390\/vaccines11030695"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1597","DOI":"10.1038\/nm.3409","article-title":"Key roles of adjuvants in modern vaccines","volume":"19","author":"Reed","year":"2013","journal-title":"Nat. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Stewart, E., Triccas, J.A., and Petrovsky, N. (2019). Adjuvant Strategies for More Effective Tuberculosis Vaccine Immunity. Microorganisms, 7.","DOI":"10.3390\/microorganisms7080255"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/nri2510","article-title":"Towards an understanding of the adjuvant action of aluminium","volume":"9","author":"Marrack","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhang, T., He, P., Guo, D., Chen, K., Hu, Z., and Zou, Y. (2023). Research Progress of Aluminum Phosphate Adjuvants and Their Action Mechanisms. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15061756"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7098","DOI":"10.1016\/j.vaccine.2014.10.036","article-title":"A novel liposomal adjuvant system, CAF01, promotes long-lived Mycobacterium tuberculosis-specific T-cell responses in human","volume":"32","author":"Joosten","year":"2014","journal-title":"Vaccine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/s41541-018-0057-5","article-title":"The TLR-4 agonist adjuvant, GLA-SE, improves magnitude and quality of immune responses elicited by the ID93 tuberculosis vaccine: First-in-human trial","volume":"3","author":"Coler","year":"2018","journal-title":"NPJ Vaccines"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2429","DOI":"10.1056\/NEJMoa1909953","article-title":"Final Analysis of a Trial of M72\/AS01(E) Vaccine to Prevent Tuberculosis","volume":"381","author":"Tait","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1056\/NEJMoa1803484","article-title":"Phase 2b Controlled Trial of M72\/AS01(E) Vaccine to Prevent Tuberculosis","volume":"379","author":"Hatherill","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Da Costa, A.C., Costa-Junior Ade, O., de Oliveira, F.M., Nogueira, S.V., Rosa, J.D., Resende, D.P., Kipnis, A., and Junqueira-Kipnis, A.P. (2014). A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112848"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"854507","DOI":"10.1155\/2015\/854507","article-title":"Th1 and Th17 Cells in Tuberculosis: Protection, Pathology, and Biomarkers","volume":"2015","author":"Lyadova","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dubois Cauwelaert, N., Desbien, A.L., Hudson, T.E., Pine, S.O., Reed, S.G., Coler, R.N., and Orr, M.T. (2016). The TLR4 Agonist Vaccine Adjuvant, GLA-SE, Requires Canonical and Atypical Mechanisms of Action for TH1 Induction. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146372"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1016\/j.celrep.2018.04.003","article-title":"STING-Activating Adjuvants Elicit a Th17 Immune Response and Protect against Mycobacterium tuberculosis Infection","volume":"23","author":"Sogi","year":"2018","journal-title":"Cell Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1476-8518-9-4","article-title":"Immunotherapeutic role of Ag85B as an adjunct to antituberculous chemotherapy","volume":"9","author":"Sheikh","year":"2011","journal-title":"J. Immune Based Ther. Vaccines"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ahmad, F., Zubair, S., Gupta, P., Gupta, U.D., Patel, R., and Owais, M. (2017). Evaluation of Aggregated Ag85B Antigen for Its Biophysical Properties, Immunogenicity, and Vaccination Potential in a Murine Model of Tuberculosis Infection. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01608"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lee, J.Y., Kim, B.-J., Koo, H.-K., Kim, J., Kim, J.-m., Kook, Y.-H., and Kim, B.-J. (2020). Diagnostic Potential of IgG and IgA Responses to Mycobacterium tuberculosis Antigens for Discrimination among Active Tuberculosis, Latent Tuberculosis Infection, and Non-Infected Individuals. Microorganisms, 8.","DOI":"10.3390\/microorganisms8070979"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.micpath.2017.08.040","article-title":"Antigen 85 complex as a powerful Mycobacterium tuberculosis immunogene: Biology, immune-pathogenicity, applications in diagnosis, and vaccine design","volume":"112","author":"Soleimanpour","year":"2017","journal-title":"Microb. Pathog."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Huygen, K. (2014). The Immunodominant T-Cell Epitopes of the Mycolyl-Transferases of the Antigen 85 Complex of M. tuberculosis. Front. Immunol., 5.","DOI":"10.3389\/fimmu.2014.00321"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/S1473-3099(24)00814-4","article-title":"Immunogenicity, safety, and efficacy of the vaccine H56:IC31 in reducing the rate of tuberculosis disease recurrence in HIV-negative adults successfully treated for drug-susceptible pulmonary tuberculosis: A double-blind, randomised, placebo-controlled, phase 2b trial","volume":"25","author":"Borges","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Tkachuk, A.P., Bykonia, E.N., Popova, L.I., Kleymenov, D.A., Semashko, M.A., Chulanov, V.P., Fitilev, S.B., Maksimov, S.L., Smolyarchuk, E.A., and Manuylov, V.A. (2020). Safety and Immunogenicity of the GamTBvac, the Recombinant Subunit Tuberculosis Vaccine Candidate: A Phase II, Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study. Vaccines, 8.","DOI":"10.3390\/vaccines8040652"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8422","DOI":"10.1038\/s41598-020-65422-1","article-title":"Vaccine adjuvant activity of a TLR4-activating synthetic glycolipid by promoting autophagy","volume":"10","author":"Chou","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1016\/j.vaccine.2012.01.074","article-title":"A TLR4 agonist synergizes with dendritic cell-directed lentiviral vectors for inducing antigen-specific immune responses","volume":"30","author":"Xiao","year":"2012","journal-title":"Vaccine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1177\/1753425918771178","article-title":"TLR agonist combinations that stimulate Th type I polarizing responses from human neonates","volume":"24","author":"Surendran","year":"2018","journal-title":"Innate Immun."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e10663","DOI":"10.1002\/btm2.10663","article-title":"Vaccine adjuvants for infectious disease in the clinic","volume":"9","author":"Goetz","year":"2024","journal-title":"Bioeng. Transl. Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kayesh, M.E.H., Kohara, M., and Tsukiyama-Kohara, K. (2023). TLR agonists as vaccine adjuvants in the prevention of viral infections: An overview. Front. Microbiol., 14.","DOI":"10.3389\/fmicb.2023.1249718"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"114020","DOI":"10.1016\/j.addr.2021.114020","article-title":"Delivery of STING agonists for adjuvanting subunit vaccines","volume":"179","author":"Feng","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12964-024-01680-0","article-title":"STING agonists as promising vaccine adjuvants to boost immunogenicity against SARS-related coronavirus derived infection: Possible role of autophagy","volume":"22","author":"Rezabakhsh","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/s41551-020-00675-9","article-title":"Prolonged activation of innate immune pathways by a polyvalent STING agonist","volume":"5","author":"Li","year":"2021","journal-title":"Nat. Biomed. Eng."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5977","DOI":"10.1021\/acs.chemrev.1c00750","article-title":"Chemical and Biomolecular Strategies for STING Pathway Activation in Cancer Immunotherapy","volume":"122","author":"Garland","year":"2022","journal-title":"Chem. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1186\/s12929-025-01144-8","article-title":"Adjunctive beneficial effect of c-di-GMP, a STING agonist, in enhancing protective efficacy of TLR4-adjuvanted tuberculosis subunit vaccine formulations","volume":"32","author":"Kwon","year":"2025","journal-title":"J. Biomed. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e108","DOI":"10.1038\/cti.2016.63","article-title":"A structure-function approach to optimizing TLR4 ligands for human vaccines","volume":"5","author":"Carter","year":"2016","journal-title":"Clin. Transl. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1038\/s41392-023-01557-7","article-title":"Vaccine adjuvants: Mechanisms and platforms","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11230","DOI":"10.1039\/C9RA00818G","article-title":"Properties of immature and mature dendritic cells: Phenotype, morphology, phagocytosis, and migration","volume":"9","author":"Kim","year":"2019","journal-title":"RSC Adv."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Grebenciucova, E., and VanHaerents, S. (2023). Interleukin 6: At the interface of human health and disease. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1255533"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Wang, H., Ruan, G., Li, Y., and Liu, X. (2025). The Role and Potential Application of IL-12 in the Immune Regulation of Tuberculosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26073106"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1046\/j.1440-1711.2001.00998.x","article-title":"Evaluation of the T cells and costimulatory molecules in the protective efficacy of 30 kDa secretory protein against experimental tuberculosis","volume":"79","author":"Yadav","year":"2001","journal-title":"Immunol. Cell Biol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Jang, D.I., and Lee, A.H. (2021). The Role of Tumor Necrosis Factor Alpha (TNF-\u03b1) in Autoimmune Disease and Current TNF-\u03b1 Inhibitors in Therapeutics. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052719"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41577-022-00746-9","article-title":"IL-17 and IL-17-producing cells in protection versus pathology","volume":"23","author":"Mills","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.cell.2006.02.019","article-title":"Translating Innate Immunity into Immunological Memory: Implications for Vaccine Development","volume":"124","author":"Pulendran","year":"2006","journal-title":"Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.immuni.2010.10.002","article-title":"Vaccine adjuvants: Putting innate immunity to work","volume":"33","author":"Coffman","year":"2010","journal-title":"Immunity"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/90609","article-title":"Toll-like receptors: Critical proteins linking innate and acquired immunity","volume":"2","author":"Akira","year":"2001","journal-title":"Nat. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1124\/pr.54.2.227","article-title":"International Union of Pharmacology. XXX. Update Chemokine Recept. nomenclature","volume":"54","author":"Murphy","year":"2002","journal-title":"Pharmacol. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e15055","DOI":"10.1016\/j.heliyon.2023.e15055","article-title":"The cytokine\/chemokine response in Leishmania\/HIV infection and co-infection","volume":"9","author":"Maksoud","year":"2023","journal-title":"Heliyon"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1016\/j.vaccine.2004.02.050","article-title":"CCR5 targeted SIV vaccination strategy preventing or inhibiting SIV infection","volume":"22","author":"Bogers","year":"2004","journal-title":"Vaccine"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: Implications for vaccine design","volume":"8","author":"Seder","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"3383","DOI":"10.1182\/blood-2011-11-370130","article-title":"Regulation of dendritic cell development by GM-CSF: Molecular control and implications for immune homeostasis and therapy","volume":"119","author":"Coffer","year":"2012","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1038\/s41467-021-24438-5","article-title":"Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5","volume":"12","author":"Zhang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3786","DOI":"10.4049\/jimmunol.178.6.3786","article-title":"IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection","volume":"178","author":"Umemura","year":"2007","journal-title":"J. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1111\/j.1365-2567.2005.02257.x","article-title":"The secreted form of the p40 subunit of interleukin (IL)-12 inhibits IL-23 functions and abrogates IL-23-mediated antitumour effects","volume":"117","author":"Shimozato","year":"2006","journal-title":"Immunology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"a016295","DOI":"10.1101\/cshperspect.a016295","article-title":"IL-6 in inflammation, immunity, and disease","volume":"6","author":"Tanaka","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1093\/intimm\/dxl007","article-title":"IL-1beta, but not IL-1alpha, is required for antigen-specific T cell activation and the induction of local inflammation in the delayed-type hypersensitivity responses","volume":"18","author":"Nambu","year":"2006","journal-title":"Int. Immunol."},{"key":"ref_66","first-page":"468","article-title":"The importance of the granulocyte-colony stimulating factor in oncology","volume":"88","author":"Cetean","year":"2015","journal-title":"Clujul Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1814620","DOI":"10.1080\/2162402X.2020.1814620","article-title":"Generation of GM-CSF-producing antigen-presenting cells that induce a cytotoxic T cell-mediated antitumor response","volume":"9","author":"Mashima","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.4049\/jimmunol.1500861","article-title":"G-CSF and GM-CSF in Neutropenia","volume":"195","author":"Mehta","year":"2015","journal-title":"J. Immunol."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/3\/214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:44:25Z","timestamp":1772448265000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/3\/214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,26]]},"references-count":68,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["vaccines14030214"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14030214","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,26]]}}}