羊种布鲁氏菌双抗原纳米结合疫苗的生物合成与免疫效果评估

黄竞, 王玉飞, 王康丰, 李淑磊, 孙鹏, 郭艳, 刘建凯, 杨瑞馥, 曾明, 潘超, 王恒樑, 朱力

工程（英文） ›› 2023, Vol. 29 ›› Issue (10) : 95-109.

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工程（英文） ›› 2023, Vol. 29 ›› Issue (10) : 95-109. DOI: 10.1016/j.eng.2023.04.007
研究论文
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羊种布鲁氏菌双抗原纳米结合疫苗的生物合成与免疫效果评估

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Biosynthesis and Immunological Evaluation of a Dual-Antigen Nanoconjugate Vaccine Against Brucella melitensis

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摘要

布鲁氏菌病是由布鲁氏菌引起的最常见的人畜共患疾病之一。然而，目前还没有供人类使用的疫苗上市。尽管一些减毒活疫苗已被批准用于动物，但保护效果并不理想。在本研究中，我们开发了一种含有多糖和蛋白质两种抗原的双抗原纳米结合疫苗来对抗布鲁氏菌感染。首先，我们使用蛋白-聚糖生物偶联技术将抗原多糖与外膜蛋白Omp19共价偶联，然后通过SpyTag/SpyCatcher系统将其装载到纳米载体上。在证实双抗原纳米结合疫苗的免疫激活能力和安全性后，我们在小鼠中通过不同的给药途径，进一步证明了疫苗免疫能够对两种抗原产生特异性血清抗体应答以及在非致死性和致死性布鲁氏菌感染模型中具有显著的保护作用。这些结果表明，双抗原纳米结合疫苗增强了辅助T细胞（Th）1和Th2免疫应答，并保护小鼠免受布鲁氏菌感染。此外，我们发现这种保护作用至少维持了18周。据我们所知，这是第一种在单个纳米颗粒上携带多种布鲁氏菌抗原（包括蛋白质和多糖）的布鲁氏菌病疫苗。因此，我们还提出了一种有吸引力的技术以共同递送不同类型的抗原，这也适用于其他传染病疫苗的制备策略。

Abstract

Brucellosis, caused by Brucella, is one of the most common zoonosis. However, there is still no vaccine for human use. Although some live attenuated vaccines have been approved for animals, the protection effect is not ideal. In this study, we developed a dual-antigen nanoconjugate vaccine containing both polysaccharide and protein antigens against Brucella. First, the antigenic polysaccharide was covalently coupled to the outer membrane protein Omp19 using protein glycan coupling technology, and then it was successfully loaded on a nano-carrier through the SpyTag/SpyCatcher system. After confirming the efficient immune activation and safety performance of the dual-antigen nanoconjugate vaccine, the potent serum antibody response against the two antigens and remarkable protective effect in non-lethal and lethal Brucella infection models were further demonstrated through different routes of administration. These results indicated that the dual-antigen nanoconjugate vaccine enhanced both T helper 1 cell (Th1) and Th2 immune responses and protected mice from Brucella infection. Furthermore, we found that this protective effect was maintained for at least 18 weeks. To our knowledge, this is the first Brucella vaccine bearing diverse antigens, including a protein and polysaccharide, on a single nanoparticle. Thus, we also present an attractive technology for co-delivery of different types of antigens using a strategy applicable to other vaccines against infectious diseases.

关键词

蛋白-聚糖偶联技术（PGCT） / 双抗原 / 纳米结合疫苗 / 羊种布鲁氏菌

Keywords

Protein glycan coupling technology (PGCT) / Dual-antigen / Nanoconjugate vaccine / Brucella melitensis

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黄竞, 王玉飞, 王康丰. 羊种布鲁氏菌双抗原纳米结合疫苗的生物合成与免疫效果评估. Engineering. 2023, 29(10): 95-109 https://doi.org/10.1016/j.eng.2023.04.007

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This work was supported by the National Key Research and Development Program of China (2021YFC2102100), the National Natural Science Foundation of China (U20A20361, 32271507, 81930122, and 82171819), and the Beijing Postdoctoral Research Foundation (2021-ZZ-035).

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