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However, they can neither induce an efficient cellular immune response, nor be frozen or lyophilized due to aggregation and diminished adjuvant efficacy. This study developed a series of lyophilizable nano\u2010aluminum adjuvants by coating nanoscale aluminum adjuvant (Adju\u2010Phos) with glycol chitosan (GCS, 20\u00a0kDa) using microfluidics technology. When the GCS\/alum weight ratio was higher than 4:1, the nano\u2010aluminum adjuvants withstood autoclaving and freeze\u2010drying treatments in the presence of trehalose without significant physicochemical changes. Moreover, the lyophilized nano\u2010aluminum adjuvants remained stable for 15 months at room temperature. When combined with HPV16 L1 virus\u2010like particles (VLPs), the nano\u2010aluminum adjuvant with 7:1 GCS\/alum weight ratio (G7\u2010A1) elicited stronger adaptive immunity, as evidenced by higher neutralizing antibodies, balanced IgG1\/IgG2c ratio, elevated IFN\u2010\u03b3\/TNF\u2010\u03b1\/IL\u20104\/IL\u201010 secretion, and increased Th1\/CTL\/memory T cell frequencies. Furthermore, combining G7\u2010A1 with MF59\u2010like emulsion or C\u2010di\u2010AMP enhanced antigen\u2010specific humoral and cellular immunity, memory T cell responses, and dendritic cell activation. These findings demonstrate the great potential of nano\u2010aluminum adjuvants in improving vaccine efficacy, and suggest that they may serve as alternatives suitable for vaccines requiring balanced Th1\/Th2 immunity or strong cellular immunity.<\/jats:p>","DOI":"10.1002\/adhm.202505300","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:12:29Z","timestamp":1781946749000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lyophilizable Thermostable Nano\u2010Aluminum Adjuvant and Combinations Induced Robust Antigen\u2010Specific Humoral and Cellular Immunity in Mice"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-3315-9205","authenticated-orcid":false,"given":"Jingying","family":"Zhou","sequence":"first","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijun","family":"Bian","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"National Engineering Laboratory for AIDS Vaccine School of Life Sciences Jilin University  Changchun China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Cui","sequence":"additional","affiliation":[{"name":"Beijing R&amp;D Center CSPC Pharmaceutical Group Co., Ltd.  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