Abstract
ABSTRACTThe 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.
Highlights
IntroductionMost people develop acute hepatitis, which is controlled by both humoral and cellular immune responses following acute infection.[1,2] around 2 to 20% of infected adults and 95% of infected newborns in Hepatitis B virus (HBV)-endemic areas fail to resolve the infection and become chronic carriers.[3,4] These individuals that remain persistently infected with HBV develop a weak and antigenically restricted antiviral immune response responsible for a chronic necroinflammatory disease
Hepatitis B virus (HBV) infection is still a major public health problem worldwide
That it is possible to subvert the immune tolerance against hepatitis B surface antigen (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
Summary
Most people develop acute hepatitis, which is controlled by both humoral and cellular immune responses following acute infection.[1,2] around 2 to 20% of infected adults and 95% of infected newborns in HBV-endemic areas fail to resolve the infection and become chronic carriers.[3,4] These individuals that remain persistently infected with HBV develop a weak and antigenically restricted antiviral immune response responsible for a chronic necroinflammatory disease. A considerable number of HBV carriers progress to more severe complications like cirrhosis and hepatocellular carcinoma.[5,6,7] On the Euroasian Journal of Hepato-Gastroenterology, January-June 2016;6(1):[25-30] contrary, current therapeutic approaches to control chronic HBV-associated hepatitis are unsatisfactory, because of its partial efficacy, high cost, and important side effects.[8,9,10]
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