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855
TIMING OF ADMINISTRATION OF ANTI-PD-1 IS IMPORTANT TO
INCREASE HBV-SPECIFIC IMMUNE RESPONSES IN AAV-HBV
MICE
Ben De Clerck1, Dorien De Pooter1, Wim Pierson2, Koen
Dockx2, Claire Evans3, Helen Horton4 and Ellen Van Gulck1,
(1)Infectious Diseases and Vaccines, J&J, (2)Charles River
Laboratories, (3)Ichor Medical Systems Inc, (4)Was Employed
By Janssen at the Time of the Study but Is No Longer Part of
the Company
Background: In chronic HBV-infected individuals,
HBV-specific immune responses are dysfunctional and
programmed cell death receptor (PD-1) is upregulated on
T-cells in periphery and liver The AAV-HBV infected mice
model was used to evaluate whether a therapeutic vaccine
can increase HBV-specific Immune responses and what
the best timing is to administer anti-PD-1 to enhance the
immunogenicity Methods: Male C57Bl/6JrJ mice, 6-8 weeks
old are infected with AAV-HBV for 28 days when chronicity
is reached All mice were vaccinated by electroporation
with pDF core and pDFpol on day 28 and on day 49 after
infection Anti-mouse PD-1 (10mg/kg) was administered on
the same time of vaccination, 1 day after the vaccination,
together with the last vaccination, 1 day after last vaccination
or 1 week after last vaccination Control mice were treated
with corresponding isotype antibody Mice were euthanized
2 weeks after last vaccination, splenocytes and intrahepatic
lymphocytes (IHL) were isolated and used in assays to
evaluate immune responses Viral parameters and ALT levels
are followed during the treatment procedure Results: Mice
treated with the therapeutic vaccine induced both splenic and
intrahepatic functional T-cells, although more than 10% of
the IHL express PD-1 on their CD8 T-cells The proliferation
capacity of intrahepatic T-cells was significantly enhanced
when anti-PD-1 was administered 1 week after the second
vaccination No effect on viral parameters could be detected
No other treatment regimens induced a significant effect
on functionality of T-cells Conclusion: Herein it is showed
that administration of anti-PD-1 one week after therapeutic
vaccination can improve the functionality of intrahepatic
lymphocytes in AAV-HBV infected mice To see an effect on
viral parameters this vaccination strategy should be combined
with agents lowering HBV s-antigen.
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发表于 2020-11-1 09:49