• 대한바이러스학회지
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• 제27권2호
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• pp.143-149
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• 1997

Most of the current licenced hepatitis B vaccines are being produced by recombinant DNA technology in large fermentation cultures of Saccharomyces cerevisiae of yeast cells which carry the gene coded for hepatitis B virus surface antigen. These vaccines are proved very effective clinically and the immunogenicity of vaccines could be maintained for a long time under refrigeration. To develope the stabilizer that could increase the stability of hepatitis B virus vaccine which could be stored for a long period at room temperature or higher conditions, glucose, lactose and sucrose solutions in phosphate buffered saline were added into hepatitis B vaccine respectively to make 2.5%, 5%, 7.5% and 10% final concentration in vaccines. These sugar-vaccine mixtures were stored at room temperature for one month, two months and three months respectively and then inoculated into ICR mice intramuscularly. On the fourteenth day after inoculation, mice were bled and sera were tested for the evaluation of efficacies of vaccines. The results showed that 5% glucose, 7.5% lactose and sucrose increased the stability of vaccines in some degree and this method could be applied for the production of other viral vaccines and bacterial vaccines.

• 대한미생물학회지
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• 제21권2호
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• pp.243-249
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• 1986

A study of the immunogenicity and reactogenicity of two doses of lot H(10, 20 mcg), two doses of lot L (20, 40 mcg) of the Smith Kline-RIT recombinant DNA yeast-derived hepatitis B vaccine and a 20-mcg dose of the Merck Sharp and Dohme plasma-derived hepatitis B vaccine was conducted in young adults under randomized, double-blind conditions. Immunization was carried out according to a 0-, 1-, and 6-month vaccination schedule. Results indicated that the yeast-derived hepatitis B vaccine was well tolerated and immunogenic. Reactogenicity to both yeast- and plasma-derived vaccines was mild in severity and low in incidence with no significant differences appearing between the study groups. One month after the third dose, the yeast-derived vaccines induced a high degree of soroconversion ranging between 95.0% and 100%. The response was not lot or dose-dependent. The administration of the plasma-derived vaccine resulted in anti-HBs geometric mean titres statistically signifirantly higher than those elicited by the different yeast-derived hepatitis B vaccines one month after the third dose of vaccine but the difference was not large enough to be of great clinical significance.

• Clinical and Experimental Pediatrics
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• 제49권1호
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• pp.14-17
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• 2006

Infants who are born prematurely or with low birth weight should be immunized at the same postnatal chronologic age. They should receive BCG, DTaP, IPV vaccines according to the same recommended schedule as full term infants. Hepatitis B vaccine schedule is modified when hepatitis B vaccine is administered a infant with birth weight less than 2,000 g. The recommended standard dose of each vaccine should be administered. Proportion of children experiencing vaccine-related adverse events dose not differ between full-term and preterm infants. Immunization with routinely recommended childhood vaccines is safe for preterm and low birth weight infants.

• Journal of Microbiology and Biotechnology
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• 제16권2호
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• pp.219-225
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• 2006

The rabbit pyrogen test and Limulus amoebocyte lysate (LAL) assay have been used to detect endotoxins present in vaccines. Currently, the rabbit pyrogen test is used to detect endotoxins in hepatitis B (HB) vaccines, even though the HB surface protein, which is the active ingredient, is overexpressed in and purified from eukaryotic cells that lack these endotoxins. Although the LAL clot assay is sensitive and reliable and can be used to replace the rabbit pyrogen test, its reaction is limited by the lack of responsiveness to the Gram-positive bacterial components. Furthermore, aluminum hydroxide in the HB vaccine can interfere with the LAL assay. In contrast, macrophages can detect the endotoxin as well as other pyrogens, and secrete $TNF-{\alpha}$. Therefore, this study was undertaken to examine the possibility of replacing the animal tests with a more efficient $TNF-{\alpha}$ secretion assay. With this in mind, we determined if aluminum hydroxide in the HB vaccines affects the $TNF-{\alpha}$ secretion assay. HB vaccines and the HB protein solutions spiked with lipopolysaccharide (LPS) produced the same level of dose-dependent $TNF{\alpha}$ secretion and temperature increase in rabbits, indicating that aluminum hydroxide in the HB vaccine does not interfere with the pyrogenic response in rabbits, nor does it interfere with $TNF-{\alpha}$ secretion. In addition, the $TNF-{\alpha}$ assay was found to be more sensitive than the LAL assay, and correlated well with the pyrogen test and the LAL assay. These results suggest that the $TNF-{\alpha}$ assay in RAW264.7 cells is a good substitute for the current pyrogen assays that are used for detecting LPS in HB vaccines as well as in other vaccines containing aluminum.

• 약학회지
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• 제57권1호
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• pp.43-54
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• 2013

Viral hepatitis is the inflammation of liver cells caused by viruses, and still one of the major health-care problems worldwide. A number of viruses to cause hepatitis are type A, B, C, D, E or G. Among these viruses leading to hepatitis, B and C are more troublesome being more prone to chronic illness which can cause the potentially fatal conditions of hepatocellular carcinoma (HCC) and/or liver failure. If immediate treatment is not initiated, liver transplant is the only option left. Over the past few decades there has been remarkable progress in diagnose and monitor all hepatitis virus infections for treatment and prevention. Nonetheless, important challenges remain to develop more effective and safe vaccines for prevention as well as antiviral agents to reduce viremia/viral load by inhibiting viral replication. The development and evaluation of antiviral agents through carefully designed clinical trials over the last 25 years has heralded a new dawn in the treatment of patients chronically infected with the hepatitis B and C viruses, but not so for the D virus. The introduction of Direct Acting Antivirals (DDAs) for the treatment of HBV carriers has permitted the long term use of these compounds for the continuous suppression of viral replication. This review aims to summarize the current status and development approaches of antiviral drugs for the treatment of viral hepatitis and future perspectives.

• Pediatric Infection and Vaccine
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• 제15권1호
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• pp.1-4
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• 2008

Immunizations are among the most cost-effective and widely used public health interventions. This is a report a revision of recommendation of immunization for children by Korean Pediatric Society. Immunization. Vaccines were divided into 4 groups. 1) Vaccines that are recommended to all infants and children (BCG, hepatitis B vaccine, DTaP, Td, Polio vaccine, Japanese encephalitis vaccine, MMR, varicella vaccine, influenza vaccine [6-23 months of age], H. influenzae type b vaccine), 2) those that can be administered to all infants and children, but decision of administration is made by parents (pneumococcal conjugate vaccine, hepatitis A vaccine, influenza vaccine [healthy children ${\geq}24$ months of age], rotavirus vaccine, human papilloma virus vaccine), 3) those that should be given to high risk group (pneumococcal polysaccharide vaccine [high risk patients ${\geq}24$ months of age], influenza vaccine [high risk patients ${\geq}24$ months of age], typhoid vaccine), and 4) those administered for control of outbreaks or prevention of emerging infectious diseases. Immunization schedule recommended by Korean Pediatric Society in 2008 is presented.

• Pediatric Infection and Vaccine
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• 제5권2호
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• pp.245-257
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• 1998

목 적 : 1983년부터 B형 간염 예방접종을 시행한 이래 국내에서 사용 중인 B형 간염 백신들의 항체 양전률에 대한 보고는 접종 일정, 접종 용량, 항체 검사 방법 및 항체 양성기준 등이 서로 상이하여 그 효과를 비교하기에 논란이 있어 왔다. 이에 저자들은 B형 간염 예방접종 후에 항체 양전률을 조사한 국내 문헌들에 대한 분석을 통해 접종되고 있는 B형 간염 백신의 효과를 맡아 보고자 하였다. 방 법 : 각과 의학회지 및 분과 학회지, 의과대학 학회지 등에서 B형 간염 백신을 접종하고 항체 양전율을 보고한 논문을 대상으로 하였다. 논문의 포함 기준은 검사 방법이 방사선 면역법 또는 효소결합 면역흡착 검사법이고 혈청 방어 항체가를 10mIU/mL 이상으로 하거나 기준 비율(sample ratio unit)를 10 ratio unit(RU) 이상으로 한 경우이며 이를 기준으로 항체 양전률을 구할 수 있는 경우로 하였다. 제외 기준은 접종 용량이 불분명하거나 불규칙한 경우, 항체 양전률이 없는 경우, 양성 기준 항체가 또는 기준 비율을 10mIU/mL 또는 10RU로 정하지 않았거나 변환할수 없는 경우, 접종 일정이 0-1-2개월 또는 0-1-6개월이 아닌 경우, 접종 백신의 기원이 명시되지 않은 경우로 하여, 52편 중 29편을 제외한 23편의 논문을 대상으로 항체 양전률을 분석하였다. 결 과 : 1) 접종 연령에 따른 항체 양전률의 가중 펑균은 Hepaccine(제일제당)의 경우 영아에서 85.1%, 소아에서 83.3%, 성인에서 62.7%로 영아와 소아에서 성인보다 항체 양전률이 높았다(P<0.01). Hepavax(녹십자)의 경우는 영아에서 84.7%, 소아에서 81.1%, 성인에서 90.8%로 소아에서 더 낮은 항체양전률을 나타내었다(P<0.01). 2) Hepavax(녹십자)를 0-1-6개월에 접종한 경우 항체 양전률의 가중 평균은 85.6%였고 0-1-2개월에 접종한 경우는 78.5%로 0-1-6개월에 접종한 경우가 항체 양전률이 더 높은 것으로 나타났다(P<0.01). 3) 영아 및 소아에서 Hepavax(녹십자)를 $5{\mu}g$ 접종한 경우와 $10{\mu}g$ 접종한 경우의 항체 양전률에는 차이가 없었다(P<0.38). 4) 성인에서 Hepaccine 접종 후 항체 양전률의 가중 평균은 62.7%. Hepavax는 90.8%였고 Engerix-B의 경우 94.8%로 Hepavax와 Engerix-B가 Hepaccine 보다 항체 양전률이 높게 나타났다(P<0.01). 결 론 : 본 조사를 동하여 만성 B형 간염 환자의 보유율이 높은 국내에서 원래 정해진 일정을 변경하는 방법은 항체 생성을 극대화하지 못하므로 주의할 필요가 있으며 백신의 면역원성을 높이기 위해서는 과거보다 더 효과적인 백신을 개발하고, 올바른 접종 방법을 지키도록 노력하여야 할 것으로 생각되었다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권4호
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• pp.311-318
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• 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.

• IMMUNE NETWORK
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• 제5권1호
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• pp.1-10
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• 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.

• Molecules and Cells
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• 제22권2호
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• pp.175-181
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• 2006

Delivery of DNA vaccines to airway mucosa would be an ideal method for mucosal immunization. However, there have been few reports of a suitable gene delivery system. In this study we used a cationic emulsion to immunize mice via the intranasal route with pCMV-S coding for Hepatitis B virus surface antigen (HBsAg). Complexing pCMV-S with a cationic emulsion dramatically enhanced HBsAg expression in both nasal tissue and lung, and was associated with increases in the levels of HBs-specific Abs in serum and mucosal fluids, of cytotoxic T lymphocytes (CTL) in the spleen and cervical and iliac lymph nodes, and of delayed-type hypersensitivity (DTH) against HBsAg. In contrast, very weak humoral and cellular immunities were observed following immunization with naked DNA. In support of these observations, a higher proliferative response of spleenocytes was detected in the group immunized with the emulsion/pCMV-S complex than in the group immunized with naked pCMV-S. These findings may facilitate development of an emulsion-mediated gene vaccination technique for use against intracellular pathogens that invade mucosal surfaces.