Cationic pH-sensitive liposome-based subunit tuberculosis vaccine induces protection in mice challenged with Mycobacterium tuberculosis

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
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Abstract

Tuberculosis (TB) has been and still is a global emergency for centuries. Prevention of disease through vaccination would have a major impact on disease prevalence, but the only available current vaccine, BCG, has insufficient impact. In this article, a novel subunit vaccine against TB was developed, using the Ag85B-ESAT6-Rv2034 fusion antigen, two adjuvants – CpG and MPLA, and a cationic pH-sensitive liposome as a delivery system, representing a new TB vaccine delivery strategy not previously reported for TB.

In vitro in human dendritic cells (DCs), the adjuvanted formulation induced a significant increase in the production of (innate) cytokines and chemokines compared to the liposome without additional adjuvants. In vivo, the new vaccine administrated subcutaneously significantly reduced Mycobacterium tuberculosis (Mtb) bacterial load in the lungs and spleens of mice, significantly outperforming results from mice vaccinated with the antigen mixed with adjuvants without liposomes. In-depth analysis underpinned the vaccine’s effectiveness in terms of its capacity to induce polyfunctional CD4+ and CD8+ T-cell responses, both considered essential for controlling Mtb infection. Also noteworthy was the differential abundance of various CD69+ B-cell subpopulations, which included IL17-A-producing B-cells. The vaccine stimulated robust antigen-specific antibody titers, further extending its potential as a novel protective agent against TB.

Abstract Image

对 pH 值敏感的阳离子脂质体结核亚单位疫苗能在受到结核分枝杆菌挑战的小鼠体内产生保护作用。
几个世纪以来,结核病(TB)一直是全球的紧急疾病,现在依然如此。通过接种疫苗预防疾病将对疾病的流行产生重大影响,但目前唯一可用的疫苗卡介苗效果不佳。本文利用 Ag85B-ESAT6-Rv2034 融合抗原、两种佐剂(CpG 和 MPLA)以及阳离子 pH 敏感脂质体作为递送系统,开发了一种新型结核病亚单位疫苗,这是一种以前从未报道过的结核病疫苗递送策略。在体外人树突状细胞(DCs)中,与不添加佐剂的脂质体相比,添加佐剂的配方诱导产生的(先天性)细胞因子和趋化因子显著增加。在体内,皮下注射新疫苗可显著减少小鼠肺部和脾脏中的结核分枝杆菌(Mtb)细菌量,明显优于接种抗原与佐剂混合但不含脂质体的小鼠。深入分析证实了疫苗在诱导多功能 CD4+ 和 CD8+ T 细胞反应方面的有效性,而这两种细胞反应都被认为是控制 Mtb 感染的关键。同样值得注意的是,各种 CD69+ B 细胞亚群的丰度不同,其中包括产生 IL17-A 的 B 细胞。疫苗激发了强大的抗原特异性抗体滴度,进一步扩大了其作为新型结核病保护剂的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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