Functionalized chitosan-G-poly caprolactone vaccine delivery system fabricated to display antigen–antibody immune complexes of Mycobacterium tuberculosis elicits immune response in Ex-vivo model

IF 2.5 Q2 MULTIDISCIPLINARY SCIENCES
Sam Ebenezer Rajadas, Vignesh Sounderrajan, Rajendran Amarnath Prabhakaran, Ragini Agrawal, Lavanya Jeyadoss, Mariappan Rajan, Krupakar Parthasarathy, Shakila Harshavardhan
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引用次数: 0

Abstract

Background

Vaccine development against tuberculosis remains a global health imperative, necessitating robust immunogenicity and safety profiles. Nanoparticle-based delivery systems offer promising avenues to enhance vaccine efficacy while ensuring tolerability. This study explores the utilization of chitosan micelles as a delivery platform for immune complex vaccination against tuberculosis. Leveraging two key antigens of Mycobacterium tuberculosis, namely HspX and Mpt51, known for their relevance in latent tuberculosis and its co-infection with the human immunodeficiency virus, immune complexes were synthesized in vitro using antibodies raised against these antigens. The immune complexes were then conjugated onto chitosan micelles, characterized for their physicochemical properties, and evaluated for their biocompatibility and immunogenicity.

Results

Chitosan nanoparticles conjugated with either antigen or its immune complexes were synthesized as micelles and physicochemical characterizations confirm the formation of micelles without altering the polymer composition. These immune complex-conjugated chitosan micelles were found to be safe, exhibiting no significant hemolytic and cytotoxic activity even at a higher concentration of 400 µg/ml. Peripheral blood mononuclear cells upon stimulation with immune complex-conjugated chitosan micelles showed enhanced cellular uptake and one to two-fold increased expression of key immune markers—interferon gamma and CD-86.

Conclusions

These findings underscore the potential of chitosan nanoparticles as a versatile delivery platform for immune complex vaccination against tuberculosis. While limitations exist, such as including only two markers of immune modulation, this study lays a foundation for future investigations into immune complex vaccine potential in animal models. In conclusion, chitosan micelles carrying immune complexes of HspX and Mpt51 tuberculosis antigens exhibit promising immunogenicity, highlighting their potential as a platform for multi-antigenic vaccine components warranting further in vivo studies.

功能化壳聚糖-G-聚己内酯疫苗递送系统可在体内外模型中显示结核分枝杆菌抗原-抗体免疫复合物并诱发免疫反应
背景针对结核病的疫苗开发仍然是全球健康领域的当务之急,它需要强大的免疫原性和安全性。基于纳米颗粒的给药系统为提高疫苗疗效、同时确保耐受性提供了很好的途径。本研究探讨了利用壳聚糖胶束作为免疫复合物疫苗接种结核病的递送平台。利用结核分枝杆菌的两种关键抗原,即 HspX 和 Mpt51(这两种抗原与潜伏结核病及其与人类免疫缺陷病毒的合并感染有关),使用针对这些抗原的抗体在体外合成了免疫复合物。结果壳聚糖纳米颗粒与抗原或其免疫复合物合成为胶束,其理化特性证实胶束的形成不改变聚合物的组成。研究发现,这些与免疫复合物结合的壳聚糖胶束是安全的,即使在 400 微克/毫升的较高浓度下也不会表现出明显的溶血和细胞毒性活性。外周血单核细胞在受到免疫复合物共轭壳聚糖胶束刺激后,细胞摄取能力增强,关键免疫标记物-γ干扰素和CD-86的表达量增加了一到两倍。虽然这项研究还存在局限性,例如只包括两种免疫调节标记物,但它为今后在动物模型中研究免疫复合物疫苗的潜力奠定了基础。总之,携带 HspX 和 Mpt51 结核病抗原免疫复合物的壳聚糖胶束表现出良好的免疫原性,突出了其作为多抗原疫苗成分平台的潜力,值得进一步进行体内研究。
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来源期刊
CiteScore
2.60
自引率
0.00%
发文量
0
期刊介绍: Beni-Suef University Journal of Basic and Applied Sciences (BJBAS) is a peer-reviewed, open-access journal. This journal welcomes submissions of original research, literature reviews, and editorials in its respected fields of fundamental science, applied science (with a particular focus on the fields of applied nanotechnology and biotechnology), medical sciences, pharmaceutical sciences, and engineering. The multidisciplinary aspects of the journal encourage global collaboration between researchers in multiple fields and provide cross-disciplinary dissemination of findings.
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