Abstract
ABSTRACTHepatitis B chronic carriage remains as a major public health problem. Protein and DNA vaccines are now widely used in therapeutic vaccine candidates. Although, the hepatitis B surface antigen (HBsAg) based vaccines have been largely studied, candidates comprising both HBsAg and core (HBcAg) either protein- or DNA-based approaches deserve further immunological characterization.In the present study, a repeated dose administration schedule for protein or DNA immunogens was conducted in order to characterize the resulting immune response in a humanized and HBsAg-tolerized setting. A novel transgenic (Tg) mice that express the HBsAg, human MHC class I (HLA-A*0201) and MHC class II (HLA-DRB1*01) molecules and devoid of endogenous murine class I and II molecules was used as a model of HBV chronic carrier. Mice were immunized by subcutaneous (protein) or intramuscular (DNA) routes and the humoral and cellular responses were evaluated.Protein or DNA immunization induced humoral immune responses against both HBsAg and HBcAg. The systematic analysis of epitopes that activate CD4+ and CD8+ T lymphocytes confirmed the accuracy of the model. Cellular immune responses were detected differing in their nature. CD8 T-cell responses were induced mostly after DNA immunization while CD4 T-cell responses were predominant in protein based immunizations. In addition, the intensity of HLA-A2-restricted CD8+ T cell responses was reduced in Tg mice expressing HBsAg when compared to control Tg mice.In conclusion, our results indicate that cellular immune responses necessary for the development of protective immunity can be achieved by DNA or protein immunization. However, important differences in their nature arise when immunogens are administered several times.How to cite this article: Mancini-Bourgine M, Guillen G, Michel ML, Aguilar JC. Impact of the Immunogen Nature on the Immune Response against the Major HBV Antigens in an HBsAg and HLA-humanized Transgenic Mouse Model. Euroasian J Hepato-Gastroenterol 2014;4(1):36-44.
Highlights
Hepatitis B virus (HBV) chronic infection remains a major public health problem
A large clinical trial evaluating the hepatitis B surface antigen (HBsAg) in formulation with a strong adjuvant suggested the use of hepatitis B care antigen (HBcAg) as the election antigen in addition to HBsAg to improve the formulation.[3]
The present work is aimed at evaluating the immunogenicity of two formulations able to induce immunity against HBsAg and HBcAg in an HLA-humanized HBsAg transgenic mouse model
Summary
Hepatitis B virus (HBV) chronic infection remains a major public health problem. More than one-third of the world population has been infected by the HBV, resulting in more than one million deaths every year as a result of a progressive hepatic disease and their complications.[1]Therapeutic vaccination has been evaluated in the treatment of chronic HBV infection. Hepatitis B virus (HBV) chronic infection remains a major public health problem. More than one-third of the world population has been infected by the HBV, resulting in more than one million deaths every year as a result of a progressive hepatic disease and their complications.[1]. Therapeutic vaccination has been evaluated in the treatment of chronic HBV infection. The fundamental role of the immune response in controlling the HBV constitutes the rationality of this approach. The target is to subvert the HBV immune-tolerance by therapeutic vaccination, but their development has proven to be difficult.[2] More potent vaccine candidates including new antigens or adjuvants as well as the study of new administration routes and the combination of immunotherapy and antivirals are required. A large clinical trial evaluating the hepatitis B surface antigen (HBsAg) in formulation with a strong adjuvant suggested the use of hepatitis B care antigen (HBcAg) as the election antigen in addition to HBsAg to improve the formulation.[3]
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