The Adoptive Transfer of HBsAG-specific Splenocytes from Balb/c Congenic Donors into HBsAg Transgenic Mice is not associated to Histographological Damage

Abstract

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.

ABX203, a novel therapeutic vaccine for chronic hepatitis B patients

“…Using the same transgenic model, a number of complementary studies on adoptive transfer of ABX203 immune splenocytes was carried out. The results obtained confirm the immunogenicity and safety profile of ABX203 vaccination strategy [22]. ABX203 formulation has been also evaluated in a humanized hepatitis B surface antigen transgenic mouse model [23,31].…”

“…Immunogenicity of ABX203 has been extensively studied in normal and transgenic mice [6,7,[20][21][22][23]. In Balb/c mice, immunogenicity of this combination formulation at different doses and antigen ratios was explored using parenteral and mucosal immunization routes [6,7,20,24].…”

“…In addition, immune response induced by ABX203 immunization was also studied in hepatitis B transgenic mice models [21][22][23]. Two different transgenic mice models of CHB were used.…”

“…Considering this point and high levels of HBsAg present in the circulation of the currently employed transgenic mice, the results pointed out the promising profile of ABX203 vaccine. Additionally, it is important to say that any potential damage that could be generated by a strong immune response in mice expressing HBsAg in their main organs, such as liver and kidneys, was evaluated in various histopathological studies (with up to 25 immunizations); no evidence of toxicity was observed [21,22,28]. Using the same transgenic model, a number of complementary studies on adoptive transfer of ABX203 immune splenocytes was carried out.…”