{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T01:41:53Z","timestamp":1792460513867,"version":"4.5.0"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2024YFC2310402"],"award-info":[{"award-number":["2024YFC2310402"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Reactivation of latent varicella-zoster virus (VZV) causes herpes zoster, which can further progress to persistent postherpetic neuralgia in a subset of patients. Rational adjuvant selection is critical for the development of recombinant VZV glycoprotein E (gE) subunit vaccines. In this study, we systematically evaluated the immunomodulatory properties of six adjuvants formulated with recombinant VZV gE in a mouse model. Multi-dimensional analyses, including innate and adaptive immunity, transcriptomics, and B-cell receptor (BCR) repertoire profiling, revealed that distinct adjuvants shape adaptive immune responses through divergent innate immune activation patterns. Traditional aluminum hydroxide and MF59 mainly induced Th2-biased humoral immunity but showed limited cellular immune activation. As TLR agonists, Poly(I:C) displayed a Th2-skewed profile with partial Th1 tendencies and exhibited oligoclonal B-cell expansion, whereas CpG 1018 potently promoted Th1 polarization and cytotoxic T-cell responses. Lipid nanoparticle (LNP) formulations drove chemokine-dependent inflammatory recruitment and facilitated dendritic cell maturation and humoral immune programming. Notably, KA101, a liposomal adjuvant containing MPL and QS-21, exhibited unique synergistic effects by inducing early IFN-\u03b3 production and simultaneously eliciting robust cellular immunity and high-titer neutralizing antibodies. Moreover, KA101 enhanced germinal center reactions, diversified the B-cell repertoire, and supported the establishment of long-term immune memory. Collectively, these findings provide mechanistic insights into adjuvant\u2013antigen interactions and establish a rational framework for developing next-generation herpes zoster subunit vaccines with potent cellular and humoral immunogenicity and durable immune memory.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1849099","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:40:24Z","timestamp":1784180424000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["KA101 outperforms other clinical adjuvants in inducing balanced Th1\/Th2 immunity and robust B cell responses to varicella-zoster virus glycoprotein E"],"prefix":"10.3389","volume":"17","author":[{"given":"Yaru","family":"Quan","sequence":"first","affiliation":[{"name":"Division of Respiratory Virus Vaccines, National Institutes for Food and Drug Control","place":["Beijing, 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