EASL2019 PS-076 JNJ-4964（AL-034 / TQ-A3334）的抗病毒活性，具有选择

StephenW

PS-076
Antiviral activity of JNJ-4964 (AL-034/TQ-A3334), a selective
toll-like receptor 7 agonist, in AAV/HBV mice after oral
administration for 12 weeks
Florence Herschke1, Chris Li2, An De Creus1, Ren Zhu2, Qinglin Han2,
Qing Lu2, Tse -I Lin3. 1Janssen Pharmaceutica NV, Beerse, Belgium;
2Janssen China RandD Center, Shanghai, China; 3Janssen Biopharma,
San Francisco, United States
Email: [email protected]
Background and aims: JNJ-64794964 (JNJ-4964), an oral toll-like
receptor 7 (TLR7) agonist in clinical development for the treatment of
chronic hepatitis B (CHB), may play an important role in restoring
immune responses to hepatitis B virus (HBV). The ability of JNJ-4964
to restore anti-HBV immune responses was assessed preclinically in
an adeno-associated virus/replicable HBV genome (AAV/HBV) mouse
model.
Method: C57BL/6 mice infected with rAAV8-1.3HBV (genotype D)
were treated orally with 20 mg/kg of JNJ-4964 weekly for 12 weeks
and followed up for 4 weeks. The anti-HBV activity of JNJ-4964, and
the capacity to induce HBV-specific immune responses, were
evaluated by T and B-cell ELIspot assays.Results: JNJ-4964 showed potent anti-HBV activity in AAV/HBV mice
treated for 12 weeks. HBV DNA and HBV surface-antigen (HBsAg)
concentrationswere undetectable for all animals 14 days after start of
treatment with no alanine aminotransferase elevations. No rebound
in HBV DNA and HBsAg was observed until the end of follow-up.
Seroconversion (HBsAg under detection limit and with detectable
anti-HBsAg antibody) was observed from 21 days after start of
treatment through to the end of follow-up by which time liver HBV
DNA and HBV RNA levels had dropped by 1.17 log10 and 0.5 log10,
respectively. Four weeks after the last dose, HBV core-antigen
expression was decreased and HBsAg became undetectable in the
liver in half of the animals. Detectable T-cell and B-cell responses
against HBsAg were observed at the end of treatment and the end of
follow-up, suggesting sustained T and B-cell immunity in JNJ-4964-
treated mice.
Conclusion: Oral administration of JNJ-4964 in AAV/HBV mice for 12
weeks resulted in potent and sustained anti-HBV activity resulting
in HBsAg seroconversion and detectable HBsAg-specific T-cell and
B-cell responses, supporting further investigation of JNJ-4964 in
patients with CHB.

StephenW

PS-076
JNJ-4964（AL-034 / TQ-A3334）的抗病毒活性，具有选择性
Toll样受体7激动剂，在口服后的AAV / HBV小鼠中
给药12周
Florence Herschke1，Chris Li2，An De Creus1，Ren Zhu2，Qinglin Han2，
清禄2，谢 - 林3。 1Janssen Pharmaceutica NV，比利时Beerse;
2Janssen中国兰德中心，中国上海; 3Janssen Biopharma，
美国旧金山
电子邮件：[email protected]
背景和目的：JNJ-64794964（JNJ-4964），口头收费
受体7（TLR7）激动剂在临床开发中的应用
慢性乙型肝炎（CHB），可能在恢复中起重要作用
对乙型肝炎病毒（HBV）的免疫反应。 JNJ-4964的能力
在临床前评估抗HBV免疫应答
腺相关病毒/可复制HBV基因组（AAV / HBV）小鼠
模型。
方法：感染rAAV8-1.3HBV的C57BL / 6小鼠（基因型D）
每周用20mg / kg JNJ-4964口服治疗12周
并随访4周。 JNJ-4964的抗HBV活性，和
诱导HBV特异性免疫反应的能力是
通过T细胞和B细胞ELIspot测定评估。结果：JNJ-4964在AAV / HBV小鼠中显示出有效的抗HBV活性。
治疗12周。 HBV DNA和HBV表面抗原（HBsAg）
开始后14天，所有动物均无法检测到浓度
没有丙氨酸氨基转移酶升高的治疗。没有反弹
在HBV DNA和HBsAg中观察到直至随访结束。
血清转换（HBsAg检出限和可检测
从开始后21天观察到抗-HBsAg抗体）
治疗到最后一次随访肝脏HBV
DNA和HBV RNA水平下降了1.17 log10和0.5 log10，
分别。最后一剂后四周，HBV核心抗原
表达减少，HBsAg在检测中无法检测到
肝脏中有一半的动物。可检测的T细胞和B细胞反应
在治疗结束时和治疗结束时观察到抗HBsAg
随访，提示JNJ-4964-持续的T细胞和B细胞免疫
治疗小鼠。
结论：JNJ-4964口服给予AAV / HBV小鼠12只
几周导致有效和持续的抗HBV活性
在HBsAg血清学转换和可检测的HBsAg特异性T细胞和
B细胞反应，支持JNJ-4964的进一步研究
CHB患者。

乙肝人1949

怎么都是小鼠