Background: Hepatitis B virus (HBV) infections remain as a major health problem. It has been estimated that about 370 million people are chronically infected worldwide. Chronic infection also increases the risk of liver diseases such as cirrhosis and hepatocellular carcinoma. Current antiviral therapies fail to control viral replication in the long term. Viral persistence has EHHQ DVVRFLDWHG ZLWK D GHIHFW LQ WKH GHYHORSPHQW RI +%9VSHFL¿F cellular immunity. The limitations of the current available therapies underline the need for alternative therapies. The development of a HBV therapeutic vaccine still remains as a feasible option of treatment despite several drawbacks. Recently, approaches like adoptive T-cell therapy have been evaluated. Materials and methods:The adoptive transfer was done intraperitoneally using Balb/c mice as donors and HBsAg-WUDQVJHQLF PLFH DV UHFHSWRUV 7KH +%V$J FRQFHQWUDWLRQ VSHFL¿F IgG response and biochemical parameters was evaluated in transgenic mice sera by ELISA. The histopathological analysis of the main organs was carried out. Results and discussion:In the present work we demonstrated WKDW WKH DGRSWLYH WUDQVIHU RI +%9VSHFL¿F FHOOXODU LPPXQLW\ GLG QR cause histopathological damage. The potent immune response transferred was developed in non-Tg Balb/c mice after multiple simultaneous intranasal and subcutaneous immunizations with NASVAC, a novel HBV therapeutic vaccine candidate. The results indicated that the transference of immunity is safe and also capable of transiently reducing the HBsAg concentration in the sera of transgenic mice. These data support the safety of the therapeutic vaccination using NASVAC and also are in line with the usefulness of the T-cell therapy for chronic hepatitis B.
The development of therapeutic vaccines against chronic hepatitis B requires the capacity of the formulation to subvert a tolerated immune response as well as the evaluation of histopathological damage resulting from the treatment. In the present study, the dynamicity of induced immune response to hepatitis B surface antigen (HBsAg) was evaluated in transgenic mice that constitutively express the HBsAg gene (HBsAg-tg mice). After immunization with a vaccine candidate containing both surface (HBsAg) and core (HBcAg) antigens of hepatitis B virus (HBV), the effect of vaccination on clearance of circulating HBsAg and the potential histological alterations were examined. Transgenic (tg) and non-transgenic (Ntg) mice were immunized by intranasal (IN) and subcutaneous (SC) routes simultaneously. A control group received phosphate-buffered saline (PBS) by IN route and aluminum by SC route. Positive responses, at both humoral and cellular levels, were obtained after five immunizations in HBsAg-tg mice. Such responses were delayed and of lower intensity in tg mice, compared to vaccinated Ntg mice. Serum IgG response was characterized by a similar IgG subclass pattern. Even when HBsAg-specific CD8+ T cell responses were clearly detectable by gamma-interferon ELISPOT assay, histopathological alterations were not detected in any organ, including the liver and kidneys.Our study demonstrated, that it is possible to subvert the immune tolerance against HBsAg in tg mice, opening a window for new studies to optimize the schedule, dose, and formulation to improve the immune response to the therapeutic vaccine candidate. These results can be considered a safety proof to support clinical developments for the formulation under study.How to cite this articleFreyre FM, Blanco A, Trujillo H, Hernández D, García D, Alba JS, Lopez M, Merino N, Lobaina Y, Aguilar JC. Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. Euroasian J Hepato-Gastroenterol 2016;6(1):25-30.
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