Enhancement of DNA vaccine-induced immune responses by a 72-bp element from SV40 enhancer.
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 Th1/Th2 balance was not obviously affected by the 72-bp element. RTV boosting further significantly enhanced DNA vaccine-primed antibody and T cell responses in a Th1-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.
Li
Hai-shan
HS
State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China.
Liu
Yong
Y
Li
Ding-feng
DF
Zhang
Ran-ran
RR
Tang
Hai-li
HL
Zhang
Yu-wei
YW
Huang
Wei
W
Liu
Ying
Y
Peng
Hong
H
Xu
Jian-qing
JQ
Hong
Kun-xue
KX
Shao
Yi-ming
YM
D016915:AIDS Vaccines / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004742:Enhancer Elements, Genetic; D005260:Female; D015683:Gene Products, gag / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010957:Plasmids; D013539:Simian virus 40 / Q000235:genetics*; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology
D016915:AIDS Vaccines; D015683:Gene Products, gag; D015483:HIV Antibodies; D007074:Immunoglobulin G; D019444:Vaccines, DNA