PMID- 29201720 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220311 IS - 2231-5047 (Print) IS - 2231-5128 (Electronic) IS - 2231-5047 (Linking) VI - 6 IP - 1 DP - 2016 Jan-Jun TI - Dynamic of Immune Response induced in Hepatitis B Surface Antigen-transgenic Mice Immunized with a Novel Therapeutic Formulation. PG - 25-30 LID - 10.5005/jp-journals-10018-1161 [doi] AB - 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 ARTICLE: Freyre FM, Blanco A, Trujillo H, Hernandez D, Garcia 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. FAU - Almeida, Freya M Freyre AU - Almeida FMF AD - Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Blanco, Aracelys AU - Blanco A AD - Animal Facilities, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Trujillo, Heidy AU - Trujillo H AD - Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Hernandez, Dunia AU - Hernandez D AD - Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Garcia, Daymir AU - Garcia D AD - Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Alba, Jose S AU - Alba JS AD - Animal Facilities, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Abad, Matilde Lopez AU - Abad ML AD - Technology Development Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Merino, Nelson AU - Merino N AD - Food and Pharmacy Faculty, University of Havana, Havana, Cuba. FAU - Lobaina, Yadira AU - Lobaina Y AD - Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. FAU - Aguilar Rubido, Julio C AU - Aguilar Rubido JC AD - Vaccine Division, Center for Genetic Engineering and Biotechnology, Havana, Cuba. LA - eng PT - Journal Article DEP - 20160709 PL - India TA - Euroasian J Hepatogastroenterol JT - Euroasian journal of hepato-gastroenterology JID - 101577625 PMC - PMC5578554 OTO - NOTNLM OT - Chronic hepatitis B OT - HBV transgenic mice OT - HBcAg OT - HBsAg OT - Therapeutic vaccine. COIS- Source of support: Center for Genetic Engineering and Biotechnology, Havana, Cuba. Conflict of interest: None EDAT- 2016/01/01 00:00 MHDA- 2016/01/01 00:01 PMCR- 2016/01/01 CRDT- 2017/12/05 06:00 PHST- 2015/11/12 00:00 [received] PHST- 2015/12/29 00:00 [accepted] PHST- 2017/12/05 06:00 [entrez] PHST- 2016/01/01 00:00 [pubmed] PHST- 2016/01/01 00:01 [medline] PHST- 2016/01/01 00:00 [pmc-release] AID - 10.5005/jp-journals-10018-1161 [doi] PST - ppublish SO - Euroasian J Hepatogastroenterol. 2016 Jan-Jun;6(1):25-30. doi: 10.5005/jp-journals-10018-1161. Epub 2016 Jul 9.