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392
Cytomegalovirus-Based HBsAg
Vaccine Induces Robust T Cell Responses and
Exerts Antiviral Effects in HBV-Replication Mice
Hongming Huang, Jia Liu and Dongliang Yang, Department
of Infectious Disease, Union Hospital, Tongji Medical College,
Huazhong University of Science and Technology
Background: Cytomegalovirus (CMV) can elicit a remarkable
impact on the immune system of their hosts. CMV-based
vaccines are currently in the spot-light as they showed superb
control of chronic viral infections and tumors growth in animal
models. Methods: In this study, we examined the potential
of using CMV as vectors for generating HBV vaccines.
BAC mutagenesis was applied to generate recombinant
mouse CMV (MCMV) expressing HBsAg under the control
of the strong eukaryotic EF1 promoter either replacing the
gene m157 or m27. To test the ability of MCMV-based HBV
vaccines against HBV, C57BL/6 mice were vaccinated either
with Δm157-MCMV-HBsAg or Δm27-MCMV-HBsAg (MCMV
replication deficiency strain), and were challenged with HBV
through hydrodynamic injection. Results: Compared to
untreated or MCMV-vaccinated control mice, mice vaccinated
with Δm157-MCMV-HBsAg or Δm27-MCMV-HBsAg showed
significantly accelerated HBV clearance in the serum and liver.
A rapid development of serum HBsAb after HBV challenge
was detected in MCMV-HBsAg vaccinated mice but not
control mice. Both MCMV and MCMV-HBsAg vaccinated mice
showed increased numbers of total lymphocytes and effector
T cells infiltration in the liver compared to untreated control
mice, however, significantly increased numbers of HBsAgspecific
CD8+ T cells in the liver was only observed in MCVMHBsAg
but not MCMV vaccinated mice. A rapid development
of robust HBsAg and HBcAg specific CD8+ T cell responses
was also observed in the liver of MCMV-HBsAg vaccinated
mice compared to control mice.Moreover, we also explored
the therapeutic effect of MCMV-HBsAg vaccines in HBV
persistent replication mice. Interestingly, only Δm27-MCMVHBsAg
but not Δm157-MCMV-HBsAg vaccination resulted in
significant HBV suppression. Combination of Δm27-MCMVHBsAg
prime and DNA boost vaccination achieved HBV
clearance in the HBV-persistent replication mice. Conclusion:
Our results demonstrated that MCMV-HBsAg vaccine could
elicit robust anti-HBV immune responses and mediate HBV
clearance in mice. Developing CMV-based vaccine against
HBV is a promising strategy for the therapeutic treatment for
chronic HBV infection.
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发表于 2018-10-11 18:55
