The effect of the parenteral route of administration on the immune response to simultaneous nasal and parenteral immunizations using a new HBV therapeutic vaccine candidate.
Chronic hepatitis B is a major health problem, with more than 350 million people infected worldwide. Available therapies have limited efficacy and require long-term continuous and expensive treatments, which often lead to the selection of resistant viral variants and rarely eliminate the virus. Immunotherapies have been investigated as a promising new approach. Several vaccine formulations have been clinically tested in chronic patients, none of which have clearly demonstrated efficacy so far. In this study we evaluated a new vaccination strategy comprising the simultaneous co-administration by the nasal and parenteral routes of a multicomponent vaccine formulation in BALB/C and HBsAg-transgenic mice. The formulation under study contains the surface and nucleocapsid antigens of the HBV, and was co-administered by the nasal route and three parenteral routes. For parenteral administration we also evaluated the immunogenicity of the antigenic mixture with alum or without the adjuvant. The immune response was evaluated by ELISA and IFN-γ ELISPOT assays. Our results indicate that all variants generated a strong antibody response in the sera against both antigens, but differed in their capacity to induce cellular immune responses against the surface antigen. Mice immunized by the nasal and subcutaneous routes without alum generated the highest IFN-γ-secreting CD8+ T-cell response, and results in this transgenic mouse model showed that there is no need to include alum. In conclusion, our results indicate that the immunization routes have to be carefully selected before carrying out clinical trials to optimize the immune response and promote further clinical development.
Lobaina
Yadira
Y
Hepatitis B Department, Biomedical Research Unit, Center for Genetic Engineering and Biotechnology, Havana, Cuba. yadira.lobaina@cigb.edu.cu
Trujillo
Heidy
H
García
Daymir
D
Gambe
Aylin
A
Chacon
Yahima
Y
Blanco
Aracelys
A
Aguilar
Julio Cesar
JC
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D017325:Hepatitis B Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000379:methods*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D000914:Antibodies, Viral; D000956:Antigens, Viral; D017325:Hepatitis B Vaccines; C041524:aluminum sulfate; D007371:Interferon-gamma