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 attainedwas 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. 作者: StephenW 时间: 2019-3-28 21:21
