• Archives of Pharmacal Research
• /
• v.29 no.11
• /
• pp.1042-1048
• /
• 2006

Plasmid DNA vaccines encoding the hepatitis B virus (HBV) surface and hepatitis C virus (HCV) envelope antigens, respectively, were constructed, and attempt were made to find the possibility of a divalent vaccine against HBV and HCV. The expression of each plasmid in Cos-1 cells was confirmed using immunocytochemistry. To measure the induced immune response by these plasmids in vivo, female BALB/c mice were immunized intramuscularly with $100\;{\mu}g$ of either both or just one of the plasmids. Anti-HBV and HCV-specific antibodies and related cytokines were evaluated to investigate the generation of both humoral and cellular immune responses. As a result, specific anti-HBV and anti-HCV serum antibodies from mice immunized with these plasmids were observed using immunoblot. The levels of IL-2 and RANTES showing a $Th_{1}$ immune response were significantly increased, but there was no change in the level of IL-4 ($Th_{1}$ immune response) in any of the immunized groups. Compared with each plasmid DNA vaccine, the combined vaccine elicited similar immune responses in both humoral and cell-mediated immunities. These results suggest that the combined DNA vaccine can induce not only comparable immunity experimentally without antigenic interference, but also humoral and $Th_{1}$ dominant cellular immune responses. Therefore, they could serve as candidates for a simultaneous bivalent vaccine against HBV and HCV infections.

• Pediatric Infection and Vaccine
• /
• v.5 no.1
• /
• pp.96-103
• /
• 1998

Purpose : We performed this study to evaluate the immune responses and protective efficacies of the HBV vaccine in infants born from hepatitis B virus(HBV) carrier mothers. Methods : Seventy eight infants born from HBV carrier mothers, who were able to follow up for 12months in the Catholic University St. Vincents hospital, were involved in this study from July 1995 to December 1996. Samples were collected at birth, 4, 8 and 12months after injection of HBIG and HBV heat-inactivated plasma derived vaccines. We evaluated the changes and relationships of viral markers detecting by enzyme immunoassay and radioimmunoassay between HBV carrier mothers and their infants. Results : 1) A total of 5.0%(106/2,117) of pregnant women were found to be a HBV carrier. The rates of HBeAg positive and negative were 38.5%(37/96) and 61.5%(59/96), respectively. 2) The seroconversion rates of anti-HBs with infants of HBV carrier mothers at 4, 8 and 12 months were 85.9%(67/78), 75.6%(59/78) and 73.1%(57/78), respectively. Although these were statistically significant differences(P<0.05), they were not related to HBeAg status of the mothers. The geometric mean titers of anti-HBs at 8 and 12 months were significantly higher than at 4 months, statistically(P<0.05). The protective efficacy of the HBV vaccine and HBIG at 12 months in infants from HBeAg positive and negative mothers were 89.8% and 100%, respectively. 3) Five of 78(6.4%) infants became infected by HBV from only HBeAg positive mothers during the follow up period of 12 months. Three of 5 infected infants became HBV carriers. HBsAg positive at birth from HBeAg positive and negative mother were 4 infants, respectively. Three of 4 infants became infected by HBV from only HBeAg positive mothers. Conclusion : We confirmed that the seroconversion rate of HBV heat-inactivated plasma derived vaccine which was one of other vaccines manufacturing in Korea was 85.9%. The protective efficacy of this HBV vaccine and HBIG at 12 months in infants from HBeAg positive and negative mothers were 89.8% and 100%, respectively.

• IMMUNE NETWORK
• /
• v.5 no.1
• /
• pp.1-10
• /
• 2005

Background: Chronic infection with hepatitis B virus (HBV) affects about 350 million people worldwide, which have a high risk of development of cirrhosis and hepatocellular carcinoma. Treatment of chronic HBV infection relies on IFN-${\alpha}$ or lamivudine. However, interferon-${\alpha}$ is effective in only about 30% of patients. Also, the occurrence of escape mutations limits the usage of lamivudine. Therefore, the development and evaluation of new compounds or approaches are urgent. Methods: We comparatively evaluated DNA and adenoviral vaccines expressing HBV antigens, either alone or in combined regimens, for their ability to elicit Th1-type immune responses in Balb / c mice which are believed to be suited to resolve HBV infection. The vaccines were tested with or without a genetically engineered IL-12 (mIL-12 N220L) which was shown to enhance sustained Th1-type immune responses in HCV E2 DNA vaccine. Results: Considering the Th1-type cytokine secretion and the IgG2a titers, the strongest Th1-type immune response was elicited by the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L. In addition, the codelivery of mIL-12 N220L modulated differentially the immune responses by different vaccination regimens. Conclusion: Our results suggest that the DNA prime-adenovirus boost regimen in the presence of mIL-12 N220L may be the best candidate for HBV vaccine therapy of the regimens tested in this study and will be worthwhile being evaluated in chronic HBV patients.

• Clinical and Experimental Pediatrics
• /
• v.51 no.7
• /
• pp.696-703
• /
• 2008

Korea is now classified as an area of intermediate endemicity for hepatitis B virus (HBV), due to the implementation of universal HBV vaccination and national preventive programs for HBV infection. A national program of HBV vaccination was launched in Korea in 1988 for school-going children and was listed on a vaccination guideline in 1991. In 1995, universal vaccination for newborn infants was started for the prevention of perinatal HBV transmission. The prevalence of HBsAg among Korean middle school students has shown marked decreased from 3.2% in the late 1990s to 0.44% in 2007. HBsAg positivity in preschool children was 0.9% in 1995, decreased to 0.2% in 2007 by national prevention program of hepatitis B vertical transmission, launched in 2002. Vaccine failure rate of HBV immunoprophylaxis is 4.2% by this program. The infected children should be monitored per 6-12 months interval. Lamivudine and interferon are approved therapies for children with chronic hepatitis B in immune-clearance phase in Korea.

• YAKHAK HOEJI
• /
• v.45 no.6
• /
• pp.708-714
• /
• 2001

Many studies have provided evidences that hepatitis B surface antigen (HBsAg) including preS region could be an ideal candidate for a new hepatitis B virus (HBV) vaccine with higher efficacy. We established CHO cell lines, IY-CHO-2 and IY-CHO-11 expressing high levels of HBsAg containing preS2 and S protein by stable transfection method. These cell lines expressed the correct size (about 1 kb in length) of HBsAg mRNA as expected. The purified protein from the culture supernatants of the clones showed the same sizes as those expressed in native hepatitis B virus (24 kDa, 27 kDa, 34 kDa and 36 kDa). Antibody productivity of CHO-derived HBsAg protein at lower dose challenge was higher than the protein containing S region alone expressed in yeast system. These results indicate that CHO-derived HBsAg protein containing preS2 and S region can be effectively used for a better immune response as a HBV vaccine.

• Journal of Preventive Medicine and Public Health
• /
• v.38 no.2
• /
• pp.170-174
• /
• 2005

Objectives: The aim of this study was to evaluate the response to a hepatitis B vaccination, and investigate the HBV DNA in subjects with isolated anti-HBc. Methods: 34 subjects with persistent isolated anti-HBc were included in the study. 32 subjects negative for HBsAg, anti-HBs and anti-HBc were included as a control group. They were all vaccinated with Hepaccine at 0, 1 and 2 months, and anti-HBs titers were measured 1 month after the 1st and 3rd vaccinations (1 and 3 months). The HBV-DNA was tested by polymerase chain reaction in subjects with isolated anti-HBc. Results: After the 1st & 3rd vaccinations, the anti-HBs titers$\geq$10mIU/ml were 70.6 & 70.6% in isolated anti-HBc group, and 34.4 & 81.2% in the control group, respectively. There were statistically significant differences after the 1st vaccination, but none after the 3rd, between the two groups. In the isolated anti-HBc and control groups, the primary, amnestic and no responses were 0 vs. 46.9%, 55.9 vs. 6.3% and 29.4 vs. 18.8%, respectively. The HBV DNA was not detected in all subjects with isolated anti-HBc. Conclusion: None of the subjects with isolated anti-HBc had a false positive result (primary response); therefore, they should be excluded from vaccination programs in Korea. To differentiate between immunity and occult infections, a single dose of vaccine, with a follow-up anti-HBs test, is preferable for subjects with isolated anti-HBc. An amnestic response indicates late immunity, and no response a suspect occult infection.

• Pediatric Infection and Vaccine
• /
• v.7 no.1
• /
• pp.136-142
• /
• 2000

Purpose : Although there are a lot of the reports about the persistence of anti HBs titer of plasma derives HBV vaccine, it is difficult to find the follow up studies of the recombinant HBV vaccine. We performed this study to compare the persistence of anti HBs titer by vaccination schedule and the seronegative rate of 5 years later according to Anti HBs titer after basic immunization in neonatal period by recombinant HBV vaccination. Methods : This study was performed on 420 neonates at Pusan Moon Hwa Hospital from April to December 1993, followed up for 5 years after basic immunization by recombinant HBV vaccine. The anti HBs titer test was done by radioimmunoassay(RIAAUSAB, Abbott laboratories). The positive anti HBs level that would protect against HBV infection was defined as a level equal to or greater than 10mIU/mL. Results : In this study the seronegative rate after 5 years was 5% in 2 month schedule group, 25.5% in 6 month schedule group(P>0.05). In 2 month schedule group the seronegative rate was 20% when anti HBs titer is lower than 200mIU/mL, 0% when more than 200mIU/mL(P>0.05). In 6 month schedule group the seronegative rate was 66.7% when anti HBs titer was lower than 200mIU/mL, 40% when 200~499.9mIU/mL, 23.9% when 500~999.9mIU/mL, 22.5% when more than 1000mIU/mL. Conclusion : In this study the seronegative rate after 5 years of recombinant HBV vaccination was 5~25.5%. The persistence of anti HBs titer was statistically irrelevant to schedule. The seronegative rate after 5 years was statistically irrelevant to anti HBs titer after basic immunization.

• Journal of Life Science
• /
• v.32 no.2
• /
• pp.94-100
• /
• 2022

Chronic infection by hepatitis B virus (HBV) greatly increases the risk for liver cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is shaped by the complex interplay of the mode of transmission, host genetic factors, viral genotype, adaptive mutations, and environmental factors. The pregenomic RNA transcription of HBV for their replication is regulated by the core promoter activation. Core promoter mutations have been the reason for acute liver failure and are associated with HCC development. We obtained HBV genes from a patient in Myanmar who was infected with HBV and identified gene variations in the core promoter region. For measuring the relative transactivation activity of the core promoter, we prepared the core-promoter reporter construct. Among the gene variations of the core promoter, the mutations of C1731T and G1806A were associated with increase in the transactivation of the HBV core promoter. Through computer analysis for searching for a tentative transcription factor binding site, we showed that the mutations of C1713T and G1806A newly created C/EBPβ and XBP1-responsive elements of the core promoter, respectively. The ectopic expression of C/EBPβ largely increased the HBV core promoter containing the C1713T mutation and that of XBP1 activated the M95 promoter containing the G1806A mutation. Our efforts to treat and prevent HBV infections are hampered by the emergence of drug-resistant mutations and vaccine-escape mutations. Our results provide the biological properties and clinical significance of specific HBV core promoter mutations.

• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.23 no.4
• /
• pp.311-318
• /
• 2020

Chronic hepatitis B viral (HBV) infection remains a major health threat, especially in high-prevalence areas. Most infants infected by mother-to-infant HBV transmission become chronic carriers. In Taiwan, many important preventive interventions have been implemented to block the perinatal transmission of HBV in the past 35 years. The first nationwide universal HBV vaccination program was launched in Taiwan in July 1984. The three-dose HBV vaccine completion rate reached 98.1% in 2018. The prevalence of Hepatitis B surface antigen (HBsAg) decreased from 9.8% in pre-vaccinated period in 1984 to 0.5% in the vaccinated cohort in 2014. The incidence of hepatocellular carcinoma in children aged 6-9 years significantly declined from 0.52 to 0.13 per 100,000 children born before and after 1984, respectively. Furthermore, we have performed a maternal HBV screening program during pregnancy since 1984, with the screening rate peaked at 93% in 2012. The HBsAg- and HBeAg-seropositive rate in pregnant women declined from 13.4% and 6.4% in 1984-1985 to 5.9% and 1.0% in 2016, respectively. To closely control perinatal HBV infection, we have administered hepatitis B immunoglobulin immediately after birth and checked the serum level of HBsAg and anti-HBs in high-risk babies born to HBsAg-seropositive mothers, irrespective of their HBeAg status, since July 2019. We have also adopted short-term antiviral treatments such as tenofovir 300 mg daily in the third trimester for highly viremic mothers and reduced the perinatal infection rates from 10.7 to 1.5%. Through all these efforts, we expect to meet the global goal of eliminating HBV infection by 2030.

• Journal of Yeungnam Medical Science
• /
• v.25 no.1
• /
• pp.1-18
• /
• 2008

Although Lamivudine and adefovir dipivoxil are efficacious drugs for preventing hepatocellular carcinoma (HCC) in chronic hepatitis B patients, their efficacy is far from completely satisfactory. The risk of liver cirrhosis and HCC begins to increase at an HBV DNA level of $10^4$ copies/ml. Even with latent or past HBV infection, episomal covalently closed circular DNA(cccDNA) plays a key rolein the persistence, relapse and resistance of HBV in its natural course or during therapy. The annual incidence of HCC in YUMC is 1.8% and 4.7% patients/year in the antiviral treatment and control groups, respectively. The ability to achieve a high rate of sustained HBV suppression with low risk of drug resistance is the ultimate goal in the treatment of chronic HBV infection. The efficacy of universal immunization with striking reductions in the prevalence of HBV in localized countries needs to be spread worldwide. With hepatitis B immunization and effective antiviral therapy, global control of HBV infection and HBV-related complications, including HCC, are possible by the end of the first half of the $21^{st}$ century.