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PS-077
Lenvervimab, a monoclonal antibody against HBsAg, can induce sustained HBsAg loss in a
chronic hepatitis B mouse model
Jung-Hwan Kim1, Hyunjin Kim1, Tae-Hee Kim1, Woohyun Kim1, Jaesung Jung1, Ara Lee1
1Mogam Institute for Biomedical Research, Youngin, Korea, Rep. of South
Email: [email protected]
Background and aims: Two billion people worldwide have been infected with hepatitis B virus (HBV)
and 240 million people live with the chronic infection. Chronic hepatitis B (CHB) patients are at high
risk of death, accounting for more than 750, 000 deaths each year. Sustained loss of HBV surface
antigen (HBsAg) is regarded as a marker for functional cure. Since HBsAg is known to suppress
immune responses against HBV, it was hypothesized that removal of HBsAg might result in restoration
of the immune responses.
Method: Therapeutic potential of Lenvervimab was evaluated in hydrodynamic injection (HDI) based
CHB mouse model with surrogate Lenvervimab (sLenvervimab) in this study.
Results: Sustained HBsAg loss for 6 months was observed after cessation of the sLenvervimab
treatment in 5 out of 12 mice (41.7%). The replication of HBV and HBV core antigen positive
hepatocytes was hardly detectable in the liver of those mice. More than 1 log reduction in the copy
number of the injected DNA (pAAV-HBV1.2), which act as a template for HBV replication as cccDNA
does in natural infection, was observed and the level attained was comparable to that of self-limited
mice. Immunohistochemistry of liver tissues showed infiltration of lymphocytes and structural changes
of hepatocytes, resembling ballooning degeneration. Also, upregulation of inflammatory markers, such
as Cox-2, interleukin-1β and prostaglandin E2, were observed. Statistically meaningful increase of
ALT level was observed in the mice. However, the level could be classified as mild or moderate. The
existence of protective immunity was confirmed by further challenge experiments to the HBsAg loss
mice.
Conclusion: These results indicated that removal of HBsAg by Lenvervimab resulted in the
restoration of immune responses against HBV and sustained HBsAg loss was caused by elimination
of HBV positive hepatocytes. This study provides proof of concept for applying antibody based
therapeutics to achieve a functional cure of CHB.
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发表于 2019-4-14 23:27
