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Micronanoparticled risedronate exhibits potent vaccine adjuvant effects [scRNA-Seq]

ABSTRACT: Nanoparticles and microparticles are widely used as vaccine adjuvants to enhance the immune response and improve the stability of antigens. While aluminum salt is one of the most common adjuvants approved for human use, its immunostimulatory capacity is suboptimal. In this study, we modified risedronate, an immunostimulant and anti‐osteoporotic drug, to create the zinc salt particle-based risedronate (Zn-RS), also termed particulate risedronate. Compared to soluble risedronate, the Zn-RS adjuvant demonstrated increased recruitment of innate cells, enhanced antigen uptake locally, and a similar antigen depot effect as aluminum salt. Furthermore, the Zn-RS adjuvant directly and quickly stimulated immune cells, accelerated the formulation of germinal centers in the lymph nodes, and facilitated the rapid production of antibodies. Importantly, the Zn-RS adjuvant exhibited superior performance in both young and aged mice, effectively protecting against respiratory diseases such as SARS-CoV-2 infection. Consequently, particulate risedronate showed great potential as a universal vaccine adjuvant, particularly beneficial for vaccines targeting the susceptible elderly.

ORGANISM(S): Mus musculus

PROVIDER: GSE239646 | GEO | 2024/08/01

REPOSITORIES: GEO

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Project description:Aluminum hydroxide, has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which allowed isoform-level analysis also. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response, cell cycle, and cellular senescence. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species.

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Micronanoparticled risedronate exhibits potent vaccine adjuvant effects [scRNA-Seq]

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