Antiviral Res. 2018 Nov 10. pii: S0166-3542(18)30256-0. doi: 10.1016/j.antiviral.2018.11.002. [Epub ahead of print]
HBV antigen and DNA loss from mouse serum is associated with novel vaccine-induced HBV surface antigen-specific cell-mediated immunity and cytokine production.
Chuai X1, Xie B2, Deng Y3, Zhao Y4, Wang W3, Gao Z4, Wang W3, Qiu X5, Tan W6.
Author information
1
MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China; Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China.
2
Capital Medical University Affiliated Beijing You'an Hospital, Beijing Institute of Hepatology, Beijing, 100069, People's Republic of China.
3
MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China.
4
Department of Pathogenic Biology, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, People's Republic of China.
5
Special Pathogens Program, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada; Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada. Electronic address: [email protected].
6
MOH Key Laboratory of Medical Virology, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, People's Republic of China. Electronic address: [email protected].
Abstract
Therapeutic vaccination is a promising strategy for controlling chronic hepatitis B virus (HBV). Here, we tested whether several novel vaccination strategies could be used to induce HBV-specific adaptive immune responses and control/eradicate HBV in a mouse model. Robust HBV antigen-specific antibody responses were elicited by several vaccination strategies using a novel particle vaccine (HBSS1), which expresses a fusion of the S (amino acids [aa] 1-223) and preS1 (aa 21-47) antigens, and/or a recombinant adenovirus rAdSS1 vaccine. However, antigen-specific cell-mediated immunity and high levels of production of multiple cytokines were elicited only by heterologous prime-boost immunization; i.e., priming with the HBSS1 vaccine followed by a rAdSS1 boost. Furthermore, the most rapid loss of serum HBsAg and HBeAg and DNA was achieved by the novel vaccination regimen (priming with HBSS1 formulated with adjuvants [alum plus PolyI:C]), which was strongly associated with more potent and functional HBsAg-specific CD4+ and CD8+ T-cell responses and increased production of interleukin (IL)-2, interferon (IFN)-γ, tumor necrosis factor-α, IL-12, and IFN-γ-induced protein (IP)-10. Thus, our novel heterogeneous prime-boost vaccine regimen shows promise as a therapeutic strategy against HBV.
KEYWORDS:
Cytokines; Hepatitis B virus; Immunity; Prime boost; Therapeutic vaccine