| Hepatitis B virus (HBV) is a noncytopathic, enveloped virus that causes acute and chronic hepatitis and hepatocellular carcinoma . The cellular immune response to HBV antigens is thought to play a critical role in the pathogenesis of the disease and in clearance of the infection. The worldwide spread of HBV is one of several most serious threats of the world public health.Some type vaccines can elicit specific cellular immune response to pathogen antigen, such as DNA vaccine, recombinant virus vaccine and virus-like particle. They have good immunotherapy effects on chronic hepatitis B. Many animal models of infectious diseases have been reported which shows DNA vaccine induced broad range of protective immunities, including antibodies, CD8+CTL,CD4+Th cells against challenge with the pathogens, such as plasmodium, influenza virus simplex virus and HIV-1.Application of this genetic vaccination approach has been extended to the treatment of cancers as well as allergic diseases and autoimmune disease. Because DNA vaccines can induce weak and short-lived immune responses in large out-bred animal, seeking for an effective way to promote the immune responses of DNA immunization is an urgent case.The use of cytokines as immunological adjuvants can enhance various immune responses when administered during the development of an immune response to a particular antigen. Interleukin-2 (IL-2) is perhaps the most extensively studied of all cytokine adjuvants. When administered as multiple injections following the antigen, IL-2 enhances the protection against challenge with the infectious agent. When used in appropriate adjuvant preparations, IL-2 has been reported to overcome MHC-linked nonresponsiveness to peptide antigens or to reverse the nonresponsiveness to HBsAg vaccination in immunocompromised patients.The adjuvant efficacy was further enhanced by physical linkage of IL-2 and antigen to ensure the cytokine effect on the local environment where immune responses occurred. Fusion proteins consisting of IL-2 with herpes simplex virus glycoprotein D or a tumor idiotypic protein have been shown to enhance immunity to the conjugated antigen and provide protection against subsequent challenge.In this study,to ensure that IL-2 was delivered at the sites of immune interactions, plasmid vector encoding the envelope protein of hepatitis B virus (HBV) was constructed and compared for its potential to induce hepatitis B surface antigen (HBsAg)-specific immune responses with vector coexpression the envelope protein and IL-2. As a contrast,we constructed a positive plasmid expressing human Interleukin-2 and coinjection with plasmid expression the envelope protein.Heterologous prime-boost immunization strategies,using sequential administration of different antigen delivery systems encoding the same epitopes or antigen, have been shown to induce enhanced and persistent levels of CD8+T cells and Th1-type CD4+T cells, which are protective against murine models of malaria. The first vector is plasmid and the second vector is virus in most present"prime-boost"immunization strategies. This approach has also been applied to animal models for a range of intracellular diseases including human immunodeficiency virus infection, Ebola virus infection, hepatitis B, and tuberculosis.Current vaccine strategies employ multiple plasmid immunizations following by recombinant live viral vectors, such as MVA,Adenovirus, Recently, heterologous prime and boost protocols have gained popularity for their ability to generate both high-frequency cellular and high-titer humoral immune responses.The abilities of Modified Vaccinia Ankara (MVA) to efficiently prime and stimulate T lymphocyte have made it a powerful therapeutic tool. A major advantage of MVA is its clear safety record. Historical development and use of MVA as vaccine against smallpox allowed to establish an extraordinary safety profile. MVA can be used under conditions of biosafety level 1 because of its avirulence and its deficiency to productively grow in human cells. In animal models, MVA vaccines have been found immunogenic and protective against various infectious agents including immunodeficiency viruses,influenza,parainfluenza,measles virus,plasmodium parasites.In our study, We have constructed recombinant DNA and MVA vaccines expressing small envelope protein, and developed a combination vaccine: DNA prime /rMVA boost regime to compare with DNA immunization only. The therapeutic effect of our combination vaccine are tested in BalB/C mice. The role of IL-2 as vaccine adjuvant for optimizing cellular immune responses is discussed in the system. The results suggest that recombinant MVA was comparable in boosting CTL responses. As a result,We found that mice injected with plasmid coexpressing envelope protein and IL-2,coinjected with plasmid expressing envelope protein and plasmid expressing IL-2 ,the activities had increased vaccine efficacy by at least 1.2-1.6 fold and induced much stronger humoral and cellular immunities to HBsAg. The HBsAg specific CTL activities were developed in the mice after rMVA immunization. The CTL activities were augmented by boosted by rMVA. The mice immunized with PBS alone did not elicited detectable HBsAg specific CTL activities. the activities of boosted by rMVA had increased at least 2 fold than immunized with pVR1012/S only, and the use of IL-2 adjuvant had increased 20%-30%than primed with pVR1012/S only and boosted by rMVA.these results indicated that the humoral and cellular response primed by DNA vaccine is efficiently boosted by recombinant MVA vaccine,and the use of IL-2 molecular adjuvant was effective and significance. The DNA Prime/rMVA Boost combination vaccines strategy in our study is effective.
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