ArticleFrontiers in immunology2026
KA101 outperforms other clinical adjuvants in inducing balanced Th1/Th2 immunity and robust B cell responses to varicella-zoster virus glycoprotein E.
Article in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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-γ 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-antigen interactions and establish a rational framework for developing next-generation herpes zoster subunit vaccines with potent cellular and humoral immunogenicity and durable immune memory.
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