Strategy Of Enhancing Immune Efficacy Elicited By DNA Vaccine

Nucleic acid vaccine is a new generation of vaccine beginning in the 90's, which has shows powerful potency in the prevention and therapy of many diseases. Because nucleic acid vaccine is a new kind of vaccine, there has been several issues unsolved, such as the diversity of immune efficacy, which is stronger in small animals, but weaker in big animals.In our study , several strategies are chosen to modulate the immune response induced by nucleic acid vaccines . (1) Genes of candidate antigens are screened . In our study, we choose Cysticercosis and tuberculosis as study models. First, challenge trial is performed in newborn pigs after cCl DNA vaccine and AgB DNA vaccine immunization. Result shows that cCl DNA vaccine induces stronger protection than that of AgB DNA vaccine. Furthermore, we find the mechanism of protection conferred by cCl DNA vaccine is the metacestode cell apoptosis. Second, we study the immune responses elicited by ESAT6, MPT64, Ag85A, HSP65 DNA vaccines in mice. (2) Adjuvants are chosen according to the character of protective immune response. In our study, Ubiquitin is chosen as an adjuvant of mycobacterium tuberculosis DNA vaccines. Results demonstrate that ubiquitin enhance the cellular immune response elicited by mycobacterium tuberculosis DNA vaccines. (3) Different inoculation formation are used. In our research, we combined ESAT6 DNA and protein expressed in E. Coli to observe the change of immune response. Results show that DNA prime-protein boost formation enhance humoral and cellular responses. However, the type of primary immune response is not changed elicited by ESAT6 DNA vaccine. (4)The influence of flanking sequence on epitope DNA vaccines are studied. In our paper, we construct epitope vaccine by choosing two CTL epitopes from MPT64 and 38kDa of M. tb and study the effect of flanking sequence on epitope presentation .Result shows that The flanking sequence-AAY enhances the presentation of MPT64 epitope , but does not change 38kDa antigen epitope presentation. These results indicate that flanking sequence can influence the presentation of CTL epitopes.