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基于自制纳米乳剂佐剂的不同疫苗抗原附着方式对全身性耐甲氧西林金黄色葡萄球菌感染的免疫反应影响

Immune response effects of diverse vaccine antigen attachment ways based on the self-made nanoemulsion adjuvant in systemic MRSA infection.

作者信息

Yang Liu-Yang, Wei Chao, Yang Yun, Tong Ya-Nan, Yang Sha, Peng Liu-Sheng, Zuo Qian-Fei, Zhuang Yuan, Cheng Ping, Zeng Hao, Zou Quan-Ming, Sun Hong-Wu

机构信息

National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University of Chinese PLA 30 Sha Ping Ba Gaotanyan Street Chongqing 400038 P. R. China

出版信息

RSC Adv. 2018 Mar 14;8(19):10425-10436. doi: 10.1039/c8ra00154e. eCollection 2018 Mar 13.

Abstract

Nanoemulsion adjuvants-based vaccines have potent induced immune responses against methicillin-resistant (MRSA) infection. However, the efficacies and immune responses of different antigen-attaching ways on self-made nanoemulsion adjuvants remain unknown. In this study, we designed three formulations of nanoemulsion adjuvants (encapsulation, mixture, and combination) to explore their immune response-enhancing effects and their underlying mechanism in a systemic infection model of MRSA. Our results showed that the three nanoemulsion-attachment ways formulated with a fusion antigen of MRSA (HlaIsdB) all improved humoral and cellular immune responses. When compared with the mixture and combination formulations, the nanoemulsion-encapsulation group effectively promoted the antigen uptake of dendritic cells (DCs) , the activation of DC in draining lymph nodes and the delayed release of antigen at injection sites . Moreover, the encapsulation group induced a more ideal protective efficacy in a MRSA sepsis model by inducing more potent antibody responses and a Th1/Th17 biased CD4 T cell response when compared with the other two attachment ways. Our findings suggested that the encapsulated formulation of vaccine with nanoemulsion adjuvant is an effective attachment way to provide protective immunity against MRSA infection.

摘要

基于纳米乳剂佐剂的疫苗对耐甲氧西林金黄色葡萄球菌(MRSA)感染具有强大的诱导免疫反应。然而,自制纳米乳剂佐剂上不同抗原附着方式的疗效和免疫反应仍不清楚。在本研究中,我们设计了三种纳米乳剂佐剂配方(包封、混合和联合),以探讨它们在MRSA全身感染模型中的免疫反应增强作用及其潜在机制。我们的结果表明,用MRSA融合抗原(HlaIsdB)配制的三种纳米乳剂附着方式均改善了体液和细胞免疫反应。与混合和联合配方相比,纳米乳剂包封组有效促进了树突状细胞(DCs)对抗原的摄取、引流淋巴结中DC的活化以及注射部位抗原的缓释。此外,与其他两种附着方式相比,包封组在MRSA败血症模型中通过诱导更强的抗体反应和Th1/Th17偏向的CD4 T细胞反应,诱导了更理想的保护效果。我们的研究结果表明,纳米乳剂佐剂疫苗的包封配方是提供针对MRSA感染的保护性免疫的有效附着方式。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/574e/9078882/ec1da9cae08e/c8ra00154e-f1.jpg

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