Poly I:C-based rHBVvac therapeutic vaccine eliminates HBV via generation of HBV-specific CD8+ effector memory T cells.
Gut
; 68(11): 2032-2043, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-30635406
ABSTRACT
OBJECTIVE:
Chronic hepatitis B (CHB) virus infection is a global health problem. Finding a cure for CHB remains a challenging task.DESIGN:
In this study, poly IC was employed as an adjuvant for HBV therapeutic vaccine (referred to as pHBV-vaccine) and the feasibility and efficiency of pHBV-vaccine in CHB treatment were evaluated in HBV-carrier mice.RESULTS:
We found that pHBV-vaccine decreased HBsAg and HBV DNA efficiently and safely in HBV-carrier mice. Further investigation showed that pHBV-vaccine promoted maturation and antigen presentation ability of dendritic cells in vivo and in vitro. This vaccine successfully restored the exhaustion of antigen-specific CD8+ T cells and partly broke the immune tolerance established in HBV-carrier mice. pHBV-vaccine also enhanced the proliferation and polyfunctionality of HBV-specific CD11ahi CD8αlo cells. Importantly, we observed that T cell activation molecule KLRG1 was only expressed on HBV specific CD11ahi CD8αlo cells. Furthermore, pHBV-vaccine reduced the expression of Eomes and increased the serum IL-12 levels, which in turn promoted the generation of effector memory short-lived effector cells (SLECs) to exhibit a critical role in HBV clearance. SLECs induced by pHBV-vaccine might play a crucial role in protecting from HBV reinfection.CONCLUSIONS:
Findings from this study provide a new basis for the development of therapeutic pHBV-vaccine, which might be a potential candidate for clinical CHB therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Poli I-C
/
Vacinas contra Hepatite B
/
Hepatite B Crônica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Gut
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
China
País de publicação:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM