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INDUCTION OF ANTI-HBS AND REDUCTION OF HBSAG BY
NASAL ADMINISTRATION OF A THERAPEUTIC VACCINE
CONTAINING HBSAG AND HBCAG (NASVAC) IN PATIENTS
WITH CHRONIC HBV INFECTION
Osamu Yoshida1, Sheikh Mohamed Fazle Akbar2, Michinori
Kohara3, Kyoko Tsukiyama-Kohara4, Takashi Miyazaki5,
Taizou Kamishita5, Mamun Mahtab6, Julio C Aguilar7,
Gerardo E Guillen7 and Yoichi Hiasa1, (1)Department
of Gastroenterology and Metabology, Ehime University
Graduate School of Medicine, (2)Department of Pathology,
Proteo-Science Center, Ehime University Graduate School
of Medicine, (3)Department of Microbiology and Cell Biology,
Tokyo Metropolitan Institute of Medical Science, (4)Joint
Faculty of Veterinary Medicine, Kagoshima University, (5)
Toko Yakuhin Kogyo Co., Ltd., (6)Department of Hepatology,
Bangabandhu Sheikh Mujib Medical University, (7)Vaccine
Division, Biomedical Research Department, Center for
Genetic Engineering and Biotechnology
Background: HBs antigen (HBsAg) loss with anti-HBs
acquisition is regarded as functional cure and recognized as
an ideal treatment goal for the patients with chronic hepatitis
B virus (HBV) infection. However, it is difficult to achieve the
functional cure in these patients by nucleos(t)ide analogs
(NAs) or interferon. Further, HBV asymptomatic carrier, not
recommended for anti-HBV therapy by current guidelines,
needs drugs for achieving functional cure, because HBV
viremia gives a risk for hepatocellular carcinoma and hepatic
flare. This study was intended to assess the efficacy of nasal
administrative therapeutic vaccine, NASVAC, containing both
HBsAg and HBcAg, on kinetics of HBsAg in CHB patient under
NAs and HBV asymptomatic carrier. Methods: CHB patient
with and HBV asymptomatic carrier enrolled in an open-label
clinical trial at Ehime University Hospital, Japan, after receiving
written consent and permission from institutional review
board and enrollment of study to the clinical trial authority of
Japan (IRB#E18-27; registered to jRCT (#jRCTs061180100)
NASVAC was emulsified in carboxyl vinyl polymer to increase
the viscosity, then administrated for 10 times, once in every
2 weeks, by a special device designed for durable existence
of NASVAC in nasal mucosa. We analyzed the data at 6
months after end of treatment (EOT) Results: Twenty nine
HBV patients under NAs treatment (NA group: age: 49-66
years, ALT: 16-28 U/L, HBsAg: 93-1942 IU/mL) and forty one
HBV carriers without active hepatitis (asymptomatic group:
age: 44-65 years, ALT: 16-29 U/L, HBsAg: 267-3267 IU/
mL) were enrolled In NA group, 78 9% of patients displayed
HBsAg reduction, and the mean HBsAg reduction was 19 9%
at 6 months after EOT 38 5% of patients showed anti-HBs
in sera Two patients in NA group received functional cure
In asymptomatic group, 85 2% of patients showed HBsAg
reduction. HBV-DNA reduction was observed in 68.2%
asymptomatic patients and 3 patients showed sustained
HBV-DNA negativity. Two patients in asymptomatic group
achieved functional cure Conclusion: NASVAC induced
anti-HBs, and reduced HBsAg in both CHB patients with NAs
and asymptomatic HBV carrier. Overall 4 patients achieved
functional cure by NASVAC. NASVAC could be a novel
immune therapy for achieving functional cure in HBV infected
patients
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发表于 2019-10-24 13:48