Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer

作     者：LI Hai-shan LIU Yong LI Ding-feng ZHANG Ran-ran TANG Hai-li ZHANG Yu-wei HUANG Wei LIU Ying PENG Hong XU Jian-qing HONG Kun-xue SHAO Yi-ming 

作者机构：State Key Laboratory for Infectious Disease Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center for Disease 100050 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2007年第120卷第6期

页      面：496-502页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：This project was supported by the CIPRA Program granted by the National Institute of Health(No.1 U19 AI51915-02) a grant from the National High Technology Research and Development Program of China(863 Program,No.2003AA219100) 

主　　题：DNA vaccines SV40 enhancer prime-boost vaccinia Tiantan strain 

摘      要：Background Although DNA vaccine is considered as the next generation of vaccine, most DNA vaccine candidates are still suffering from the relatively weak immunogenicity despite the increased dosage of plasmid DNA administered. In order to enhance the immune responses elicited by a codon-optimized HIV gag DNA vaccine, a modified plasmid vector pDRVI1.0 and a booster immunization with replicating Tiantan vaccinia （RTV） strain expressing the same gene were employed. Methods Vector pDRVI1.0 was constructed through inserting the 72-bp element from the SV40 enhancer, which was reported promoting nuclear transport of plasmid DNA, to the upstream of cytomegalovirus enhancer/promoter region of the plasmid vector pVR1012. Gene expression levels from expression plasmids based on pDRVI1.0 and pVR1012 were tested. Humoral and cellular immune responses induced by DNA vaccine alone or DNA prime-RTV boost regimen were determined in mice. Results It was shown that the 72-bp element significantly enhanced the gene expression level in non-dividing cells. gag-specific humoral and cellular immune responses induced by DNA vaccination were both significantly improved, while the Thl/Th2 balance was not obviously affected by the 72-bp element. RTV boosting further significantly enhanced DNA vaccine-palmed antibody and T cell responses in a Thl-biased manner. Conclusions The 72-bp SV40 enhancer element should be included in the DNA vaccine vector and RTV strain is a very efficient live vector for boosting immunization.