{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T05:11:01Z","timestamp":1788844261179,"version":"build-2803163510"},"reference-count":24,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Shenzhen Medical Research Fund","award":["D2401001"],"award-info":[{"award-number":["D2401001"]}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2025A1515012065"],"award-info":[{"award-number":["2025A1515012065"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"crossref","award":["2023A1515110428"],"award-info":[{"award-number":["2023A1515110428"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20240813142059020"],"award-info":[{"award-number":["JCYJ20240813142059020"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32500829"],"award-info":[{"award-number":["32500829"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32500829"],"award-info":[{"award-number":["32500829"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: Aluminum-adjuvanted hepatitis B vaccines effectively prevent primary HBV infection but predominantly favor humoral immunity and have limited capacity to induce strong cellular responses. To improve immune-response quality, we developed a Ganoderma lucidum polysaccharide-modified hybrid nanoparticle adjuvant (GHNP) for hepatitis B surface antigen (HBsAg) vaccination. Methods: Cationic PEG-PCL\/DOTAP hybrid nanoparticles (HNPs) were surface-modified with Ganoderma lucidum polysaccharide (GLP) at different mass ratios and characterized by particle size, polydispersity index, zeta potential, and transmission electron microscopy. Antigen uptake, RAW264.7 cell viability, MHC II expression, and TLR2\/4-associated TNF-\u03b1 secretion were evaluated in vitro. C57BL\/6 mice were immunized intramuscularly with PBS, HBsAg, HBsAg + Aluminum, HBsAg@HNP, or HBsAg@GHNP6 on Days 0, 14, and 28. HBsAg-specific antibodies, splenocyte activation, proliferation, and cytokine secretion were assessed. Results: GHNP6 showed suitable physicochemical properties, acceptable cytocompatibility at concentrations up to 10 \u03bcg\u00b7mL\u22121, and efficient model-antigen uptake. GHNP increased MHC II expression in RAW264.7 cells, and TLR2\/4 inhibition reduced nanoparticle-associated TNF-\u03b1 secretion, supporting involvement of these pathways in immune activation. In vivo, HBsAg@GHNP6 induced robust HBsAg-specific IgG responses and a higher IgG2a\/IgG1 ratio than HBsAg@HNP and HBsAg + Aluminum. It also produced the highest splenocyte proliferation after HBsAg restimulation, with lower IL-6 secretion than HBsAg + Aluminum and moderately increased IFN-\u03b3 compared with PBS and free HBsAg. Conclusions: GHNP integrates nanoparticle-assisted antigen delivery with GLP-mediated immunomodulation and represents a promising strategy for enhancing cellular immune responses while maintaining humoral immunity in HBsAg vaccination.<\/jats:p>","DOI":"10.3390\/vaccines14090779","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T12:12:25Z","timestamp":1788783145000},"page":"779","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Ganoderma lucidum Polysaccharide-Modified Nanoadjuvant Elicits Potent Cellular Immunity for Hepatitis B Vaccine"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhe","family":"Zhai","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Institute for Inheritance-Based Innovation of Chinese Medicine, Marshall Laboratory of Biomedical Engineering, School of Pharmacy, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"given":"Jiansong","family":"You","sequence":"additional","affiliation":[{"name":"R&D Center, Aim Honesty Biopharmaceutical Co., Ltd., Dalian 116620, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4911-7165","authenticated-orcid":false,"given":"Xuhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Chinese Medicine Ingredients and Gut Microbiomics, Institute for Inheritance-Based Innovation of Chinese Medicine, Marshall Laboratory of Biomedical Engineering, School of Pharmacy, School of Basic Medical Sciences, Shenzhen University Medical School, Shenzhen University, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41575-023-00760-9","article-title":"Global burden of hepatitis B virus: Current status, missed opportunities and a call for action","volume":"20","author":"Hsu","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1146\/annurev-virology-091919-062728","article-title":"Prospects for the Global Elimination of Hepatitis B","volume":"8","author":"Block","year":"2021","journal-title":"Annu. Rev. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/j.vaccine.2011.12.116","article-title":"Global epidemiology of hepatitis B virus infection: New estimates of age-specific HBsAg seroprevalence and endemicity","volume":"30","author":"Ott","year":"2012","journal-title":"Vaccine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1002\/jps.22284","article-title":"Vaccines with aluminum-containing adjuvants: Optimizing vaccine efficacy and thermal stability","volume":"100","author":"Clapp","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_5","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_6","doi-asserted-by":"crossref","first-page":"S343","DOI":"10.1093\/infdis\/jiaa668","article-title":"Hepatitis B vaccines","volume":"224","author":"Pattyn","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6186","DOI":"10.4049\/jimmunol.0901474","article-title":"AS04, an aluminum salt- and TLR4 agonist-based adjuvant system, induces a transient localized innate immune response leading to enhanced adaptive immunity","volume":"183","author":"Didierlaurent","year":"2009","journal-title":"J. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s12951-023-01989-x","article-title":"Nanovaccine-based strategies for lymph node targeted delivery and imaging in tumor immunotherapy","volume":"21","author":"He","year":"2023","journal-title":"J. Nanobiotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Cui, M., Liu, Y., Ma, Z., Xi, J., Tian, Y., Hu, J., Song, C., Fan, L., and Li, Q. (2024). Uptake quantification of antigen carried by nanoparticles and its impact on carrier adjuvanticity evaluation. Vaccines, 12.","DOI":"10.3390\/vaccines12010028"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/j.tibtech.2022.03.011","article-title":"Nano toolbox in immune modulation and nanovaccines","volume":"40","author":"Azharuddin","year":"2022","journal-title":"Trends Biotechnol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41541-025-01253-3","article-title":"Trehalose-loaded LNPs enhance mRNA stability and bridge in vitro in vivo efficacy gap","volume":"10","author":"Liu","year":"2025","journal-title":"npj Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.cell.2020.02.058","article-title":"Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein","volume":"181","author":"Walls","year":"2020","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1016\/j.phytochem.2006.07.004","article-title":"Ganoderma\u2014A therapeutic fungal biofactory","volume":"67","author":"Paterson","year":"2006","journal-title":"Phytochemistry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1039\/D2FO01683D","article-title":"Therapeutic potential and nutritional significance of Ganoderma lucidum\u2014A comprehensive review from 2010 to 2022","volume":"14","author":"Swallah","year":"2023","journal-title":"Food Funct."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.carbpol.2013.10.087","article-title":"Immunostimulatory activities of \u03b2-d-glucan from Ganoderma lucidum","volume":"102","author":"Wang","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1124\/mol.106.022327","article-title":"Polysaccharide purified from Ganoderma lucidum induces gene expression changes in human dendritic cells and promotes T helper 1 immune response in BALB\/c mice","volume":"70","author":"Lin","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Zhong, Y., Tan, P., Lin, H., Zhang, D., Chen, X., Pang, J., and Mu, R. (2024). A review of Ganoderma lucidum polysaccharide: Preparations, structures, physicochemical properties and application. Foods, 13.","DOI":"10.3390\/foods13172665"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gao, Y., and Guo, Y. (2023). Research progress in the development of natural-product-based mucosal vaccine adjuvants. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1152855"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"125183","DOI":"10.1016\/j.carbpol.2026.125183","article-title":"Virus-inspired Ganoderma lucidum polysaccharide-functionalized adjuvant with pseudo-zwitterionic interface for potentiated nasal immunization","volume":"381","author":"Liu","year":"2026","journal-title":"Carbohydr. Polym."},{"key":"ref_20","unstructured":"(2018). Laboratory Animal\u2014Guideline for Ethical Review of Animal Welfare (Standard No. GB\/T 35892-2018)."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/s41392-024-01757-9","article-title":"NF-\u03baB in biology and targeted therapy: New insights and translational implications","volume":"9","author":"Guo","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Jang, D., Lee, A.-H., Shin, H.-Y., Song, H.-R., Park, J.-H., Kang, T.-B., Lee, S.-R., and Yang, S.-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_24","doi-asserted-by":"crossref","unstructured":"Mussbacher, M., Derler, M., Bas\u00edlio, J., and Schmid, J.A. (2023). NF-\u03baB in monocytes and macrophages\u2014An inflammatory master regulator in multitalented immune cells. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1134661"}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/779\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:32:32Z","timestamp":1788841952000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/779"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":24,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["vaccines14090779"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14090779","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]}}}