PAMAM-Lys, a novel vaccine delivery vector, enhances the protective effects of the SjC23 DNA vaccine against Schistosoma japonicum infection.
PAMAM-Lys, a novel vaccine delivery vector, enhances the protective effects of the SjC23 DNA vaccine against Schistosoma japonicum infection.
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新型疫苗递送载体 PAMAM-Lys 增强 SjC23 DNA 疫苗对日本血吸虫感染的保护作用
DOI：
10.1371/journal.pone.0086578
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Wang X;Dai Y;Zhao S;Tang J;Li H;Xing Y;Qu G;Li X;Dai J;Zhu Y;Zhang X
背景日本血吸虫病仍然是中国一个主要的公共卫生问题。吡喹酮类化疗可有效降低感染和强度；然而，它不能防止再次感染。此外，在流行地区长期反复使用吡喹酮后，人们越来越关注吡喹酮耐药性。因此，开发血吸虫病疫苗作为预防和控制日本血吸虫病的一项战略，受到高度重视。本研究旨在开发PAMAM树状大分子作为日本血吸虫病DNA疫苗的新型疫苗载体，并评价其增强日本血吸虫感染保护作用的能力。采用赖氨酸对4.0G PAMAM进行改性，合成了改性产物PAMAM- lys。PAMAM-Lys具有较高的转染率和较低的细胞杀伤能力。在小鼠模型中，与裸DNA疫苗相比，结合PAMAM-Lys的DNA疫苗对日本血吸虫感染具有更高的保护水平。此外，PAMAM-Lys联合DNA疫苗免疫小鼠的抗体显著高于裸DNA疫苗免疫小鼠的抗体。PAMAM-Lys载体引发了主要的IgG2a抗体反应，并极大地增加了IL-2和IFN-γ的产生。结论/意义赖氨酸修饰的PAMAM-Lys是一种优良的载体。PAMAM-Lys可增强DNA疫苗的免疫反应性，增强SjC23 DNA疫苗对日本血吸虫感染的保护作用。
Background Schistosomiasis japonica remains a major public-health concern in China. Praziquantel-based chemotherapy effectively reduces both infections and intensity; however, it can not prevent re-infection. Furthermore, there is an increasing concern about praziquantel resistance following long-term repeated use of the drug in endemic areas. Therefore, development of a schistosomiasis vaccine, as a strategy to prevent and control schistosomiasis japonica, has been given high priority. The present study was conducted to develop PAMAM dendrimers as a novel vaccine delivery vector for a schistosomiasis japonica DNA vaccine and evaluate its ability to enhance protective effects against Schistosoma japonicum infection. Methodology/Principal Findings Lysine was used to modify 4.0G PAMAM, and the modified product PAMAM-Lys was synthesized. PAMAM-Lys showed both high transfection and low cytotocity for gene delivery in vitro. DNA vaccines combined with PAMAM-Lys produced higher level of protection compare with naked DNA vaccines against S. japonicum infection in a mouse model. Futhermore,antibodies from mice immunized with PAMAM-Lys combined DNA vaccines were significantly higher than those of mice immunized with the naked DNA vaccines. The PAMAM-Lys vector elicited a predominantly IgG2a antibody response and a tremendously increase in the production of IL-2 and IFN-γ. Conclusion/Significance Lysine-modified PAMAM-Lys is an excellent vector. PAMAM-Lys may enhance the immunoreactivity of DNA vaccine and increase the protective effect of the SjC23 DNA vaccine against S. japonicum infection.
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影响因子：
2.6
作者：
Bickle, QD;Bogh, HO;Zhang, YB
通讯作者：
Zhang, YB
影响因子：
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作者：
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通讯作者：
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影响因子：
2.1
作者：
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影响因子：
5.5
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
McManus, DP