期刊
ANTIVIRAL RESEARCH
卷 119, 期 -, 页码 68-77出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.antiviral.2015.04.015
关键词
Coxsackievirus B3; Chronic myocarditis; DNA vaccine; AIM2; Chitosan; Multifunctional CD8(+) T cells
资金
- Major State Basic Research Development Program of China [2013CB530501]
- National Natural Science Foundation of China [31470880, 31170878]
- natural science foundation of the Jiangsu higher education institutions [12KJB310015]
- Jiangsu 333 project of cultivation of high-level talents and Jiangsu Provincial Innovative Team
- Qing Lan Project of the Jiangsu higher education institutions
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
Coxsackievirus B3 (CVB3) infection can cause acute myocarditis and chronic myocarditis, leading to dilated cardiomyopathy (DCM) with no effective therapeutic strategy. Therefore, we investigated the potential of absent in melanoma 2 (AIM2) to enhance the therapeutic efficacy of DNA vaccine against CVB3-induced chronic myocarditis. Mice were infected with CVB3 and then intranasally immunized with chitosan-pcDNA3.1 (mock), chitosan-pAIM2 (CS-pAIM2), chitosan-pVP1 (CS-pVP1), or chitosan-pAIM2 plus chitosan-pVP1 (CS-pAIM2/CS-pVP1) at 7, 21, and 35 d. Therapeutic efficacies of various vaccines were evaluated at day 56 d. Compared with CS-pVP1 immunization, CS-pAIM2/CS-pVP1 co-immunization significantly increased survival rate, improved cardiac function, as well as decreased myocardial injury and fibrosis, this result indicated that CVB3-induced chronic myocarditis was alleviated. CVB3-specific T lymphocyte proliferation and cytotoxic T lymphocyte responses of the CS-pAIM2/CS-pVP1 co-immunization group were also increased. More interestingly, CS-pAIM2/CS-pVP1 co-immunization could facilitate CVB3-specific multifunctional CD8(+) T cell induction in the intestinal mucosa, and this induction was closely correlated with myocardial scores, this result indicated that CS-pAIM2/CS-pVP1 vaccine exhibits therapeutic efficacy by enhancing multifunctional CD8(+) T cells. This study may represent a novel therapy for CVB3-induced chronic myocarditis. (C) 2015 Elsevier B.V. All rights reserved.
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