Effect of therapeutic dual-plasmid HBV DNA vaccine on immune function in cancrivorous monkeys / 解放军医学杂志

ABSTRACT

Objective To investigate the effect of therapeutic dual-plasmid HBV DNA vaccine on specific humoral and cellular immunity in cancrivorous monkey (Macaca fascicularis). Methods The eukaryotic expression plasmids encoding human IL-2 and IFN-? fusion protein (pFP) were constructed to enhance the cellular immunity of therapeutic HBV DNA vaccine (pS2.S) encoding HBV envelope middle protein in the form of dual-plasmid (pS2.S+pFP). Thirty cancrivorous monkeys were randomly divided into 5 groups (6 each) with sex rotio of 1∶1, namely the dual-plasmid DNA vaccine group in high dosage (2000?g/kg), medium dosage (660?g/kg), low dosage (200?g/kg), and EP-mediated pFP (330?g/kg) or PBS administration groups as the controls. The monkeys were vaccinated repeatedly with the dual-plasmid HBV DNA vaccine, and then the immune responses including level of serum anti-HBs and number of IFN-? secreting T-cells induced by HBsAg were examined by means of enzyme-linked immunosobent assay (ELISA) and enzyme-linked immunosobent spot assay (ELISPOT) respectively. Results Ten weeks after immunization of HBV DNA vaccine, various levels of serum anti-HBs was detected in all the monkeys of three different dose groups. Sixteen weeks after administration of EP-mediated HBV DNA vaccine, the positive HBsAg-specific INF-? T cell responses was found in 3, 2 and 3 out of 3 monkeys, respectively in the high, medium and low losage groups, and HBsAg-specific INF-? T cell responses were positive in all the animals with the respective cell count of 30.0?13.5 SFCs/3?105 PBMCs, 30.7?26.3 SFCs/3?105 PBMCs and 17.7?6.4 SFCs/3?105 PBMCs in each corresponding group at the 29th week. However, HBsAg-specific INF-? T cell responses were negative in the pFP and PBS group at the same time. Conclusion Electroporation-mediated vaccination of the HBV DNA vaccine can effectively induce both humoral and cellular HBsAg-specific immune responses in cancrivorous monkeys.