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LB-14
A Nasal Administrative Therapeutic Vaccine
(NASVAC) with Modified Treatment Strategy
Reduces and Eliminates Hbs Antigen in HBV
Infected Patients with or without Nucleos(t)Ide
Analogs Therapy
Dr. Osamu Yoshida1, Dr. Yusuke Imai1, Dr. Sheikh
Mohamed Fazle Akbar2, Dr. Michinori Kohara3, Prof. Kyoko
Kohara4, Dr. Takashi Miyazaki5, Dr. Taizou Kamishita5, Prof.
Mamun Mahtab6, Dr. Julio Cesar Aguilar7, Prof. Gerardo
Enrique Guillen7 and Prof. Yoichi Hiasa1, (1)Department of
Gastroenterology and Metabology, Ehime University Graduate
School of Medicine, (2)Department of Pathology, 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: Clearance of HBs antigen (HBsAg) is recognized
as an ideal long-term treatment goal for patients with hepatitis
B virus (HBV) infection. However, the present regimen with
nucleos(t)ide analogs (NUCs) is difficult to achieve the goal. A
therapeutic vaccine, which contains both HBsAg and HBcAg
(NASVAC, Center for Genetic Engineering and Biotechnology,
CIGB, Havana, Cuba) displayed therapeutic effects to reduce
the amount of HBV-DNA by both nasal and subcutaneous
administration. In this study, we have modified the treatment
strategy, and evaluate its potentials to reduce and eliminates
HBsAg in chronic HBV infection. Methods: HBV infected
patients with or without taking NUCs were enrolled in an openlevel
clinical trial at Ehime University Hospital in Japan after
receiving written consent of the patients. In order to increase
the immunogenic capacity of NASVAC, we emulsified
NASVAC was mixed with carboxyl vinyl polymer (TOKO
Yakuhin, Toyama, Japan) to increase the viscosity, and
used a special device to spray the wide area of nasal cavity.
Besides, we administered NASVAC only via nasal route for
10 times every 2 weeks. Then, we analyzed data at the end
of treatment (EOT) and at 6 months after EOT. This trial is
approved by the Institutional Review Board (IRB#1609017)
and registered to UMIN-CTR (#UMIN000027442). Results:
Twenty three HBV patients with NUCs therapy (wNUCs; age:
54 years (49-64), male/female: 16/7, ALT: 19 (16-27) U/L,
HBsAg: 436 (229-1853) IU/mL) and 31 HBV patients without
NUCs therapy (w/oNUCs; age: 56(45-66), male/female:
15/16, ALT: 21(16-27) U/L, HBsAg: 1370(101-3469) IU/mL)
were enrolled in this trial. Twelve patients in wNUCs and 5
patients in w/oNUCs completed 6 months follow-up after EOT.
9.3% of enrolled patients had a temporal nasal discomfort,
however, any other adverse events, as well as elevation of
ALT, were not observed during the treatment. The reduction of
HBsAg were observed in 11 of 12 (91.7%) of wNUCs patients
and in 5 of 5 (100%) of w/oNUCs patients at 6 months after
EOT. The amount of HBsAg reduction was 23.5% (Mean
value) in wNUCs patients, and 44.1% in w/oNUCs patients.
Antibody to HBsAg (anti-HBs) was detected in 3 of 12 (25%)
of wNUCs patients, and in 2 of 5 (40%) of w/oNUCs patients.
Remarkably, latest data indicated that 2 w/oNUCs patients
and 1 wNUCs patient have achieved clearance of HBsAg and
acquisition of anti-HBs with sustained HBV-DNA negative.
Conclusion: NASVAC with the modified treatment strategy
has a potential to reduce or eliminate HBsAg in patients with
HBV infection. The study is continuing, and more than 35
patients are now under treatment or follow-up. At the Meeting,
we would present the latest data. |
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发表于 2018-12-6 14:41
