丰城市某镇2000-2009年乙肝疫苗接种概况及乙肝流行病学分析

目的:分析尚庄街办2000年-2009年乙肝疫苗接种、乙肝发病率、1-15岁人群乙肝免疫状况。方法:对尚庄2000年-2009年乙肝接种资料、发病资料、免疫状况进行流行病学分析。结果:乙肝疫苗接种率已提高、发病率下降、乙肝表面抗体阳性率随年龄增加而下降。结论:控制乙肝发生的主要方法应当是加强乙肝疫苗接种、管理好乙肝表面抗原阳性人群。

New therapeutic vaccination strategies for the treatment of chronic hepatitis B

Chronic hepatitis B virus(CHB) is currently treated with either interferon-based or nucleot(s)idebased antiviral therapies.However,treatment with pegylated interferon alpha results in a durable antiviral response in only about 30%patients and is associated with side effects.Most patients receiving nucleot(s)ide analogue treatment do not establish long-term,durable control of Infection and have rebounding viremia after cessation of therapy.Thus,novel therapy strategies are necessary to achieve the induction of potent and durable antiviral immune responses of the patients which can maintain long-term control of viral replication.Therapeutic vaccination of HBV carriers is a promising strategy for the control of hepatitis B.Here the authors review new therapeutic vaccination strategies to treat chronic hepatitis B which may be introduced for patient treatment in the future.

Identification of the immunogenic domains in HBsAg preS1 region using overlapping preS1 fragment fusion proteins

AIM: The incorporation of hepatitis B virus (HBV) preS1 region into epitope-based vaccines against HBV has been accepted widely, but the incorporate site and size of preS1 sequence is controversial. Therefore our purpose was to further investigate its immunogenic domains for the epitopebased hepatitis B vaccine design.METHODS: Eight GST fusion proteins containing overlapping preS1 fragments in preS1 (21-119) region were expressed in E.coli. Using these purified fusion proteins, the immunogenic domains in preS1 region were identified in detail in mice and humans by Western blot analysis and ELISA.RESULTS: The results in mice showed that the immunogenic domains mainly existed in preS1 (21-59) and preS1 (95-109). Similarly, these fragments had strong immunogenicity in humans; whereas the other parts except for preS1 (60-70) also had some immunogenicity.More importantly, a major immunogenic domain, preS1 (34-59), which has much stronger immunogenicity, was identified. Additionally, the antibodies against some preS1 fragments, especially preS1 (34-59), were speculated to be virus-neutralizing.CONCLUSION: Eight GST fusion proteins containing overlapping preS1 fragments were prepared successfully. They were used for the study on the immunogenic domains in preS1 (21-119) region. The preS1 (34-59) fragments were the major immunogenic domains in the preS1 region, and the antibodies against these fragments were speculated to be virus-neutralizing. Therefore, the incorporation of preS1 (34-59) fragments into epitopebased HBV vaccines may be efficient for enhancement of immune response. Additionally, the results also imply that there are more complex immune responses to preS1 region and more abundant immunogenic domains in humans.

Immune response to an indigenously developed r-Hepatitis B vaccine in mixed population: Study of an accelerated vaccination schedule

AIM: To establish the safety and efficacy of an indigenously developed r-hepatitis B vaccine using an accelerated schedule and to highlight the social awareness and commitment in preventing the spreading of hepatitis B virus infection. METHODS: The study was a multicentric, double blind, randomized (3:1) study using three doses of vaccine immunization schedule (20μg for those above 10 years old and 10 μg for those below 10 years old) on d 0, 30 and 60. One hundred and sixty-six subjects were enrolled (87 males and 76 females aged 5-35 years). The main outcome measure was assessment of immunogenicity and safety. RESULTS: A 100% seroconversion response was observed on the 30th d after the 1st injection in both the experimental groups. The sero-protection data reported a 41.2-65.6% response on the 30th d after the 1st injection and reached 100% on the 60th d. Descriptive statistical analysis showed a geometric mean titer value of 13.77 mIU/mL in the test (BEVAC) group and 10.95 mlU/mL in the commercial control (ENGERIX-B) group on the 30th d after the 1st injection. The response on the 60th d showed a geometric mean titre value (GMT) of 519.84 mlU/mL in the BEVAC group and 475.46 mlU/mL in the ENGERIX-B group. On the 90th d, the antibody titer response was observed to be 2627.58 mlU/mL in the BEVAC group and 2272.72 mlU/mL in the ENGERIX-B group. Two subjects in each group experienced pains at injection site after the first vaccination. A total of six subjects in both groups experienced a solicited adverse reaction, which included pains, swelling and redness at the injection site, three subjects in the group-B had a pain at the injection site after the third dose. No other serious adverse events occurred and no dose-related local or general symptoms were observed during the study. CONCLUSION: The vaccine is safe, efficacious and immunogenic in comparison with the well documented ENGERIX-B.

T cell responses to hepatitis B surface antigen are detectable in non-vaccinated individuals

AIM: To evaluate, whether humoral hepatitis-B-vaccine non-responders also fail to mount a T cell response and to compare these results to normal vaccinees. METHODS: Fourty-seven health care employees were enrolled in this study including all available non- responders (n = 13) with an anti-HBsAg titer < 10 kU/L and all available low-responders (n = 12) with an anti- HBsAg titer < 100 kU/L. Also, 12 consecutive anti-HBsAg negative pre-vaccination subjects were enrolled as well as 10 subjects (+7 from the vaccinated group) with titers > 1000 kU/L as controls. PBMC from all subjects were analyzed by IFN-γ and IL-4 ELISPOT assays for the presence of hepatitis B surface antigen (HBsAg) reactive T cells. RESULTS: Non-responders and low-responders had no or only very limited T cell responses, respectively. Indi- viduals responding to vaccination with the induction of a high anti-HBsAg titer showed a strong T cell response after the third vaccination. Surprisingly, these individuals showed response even before the first vaccination. T cell response to control antigens and mitogens was similar in all groups. CONCLUSION: Our data suggest that there is no gen- eral immune deficiency in non-/low-responders. Thus, we hypothesize that the induction of anti-HBsAg re- sponses by vaccination is significantly dependent on the pre-existing T cell repertoire against the specific antigen rather than the presence of a general T cell defect.

Therapeutic effect of autologous dendritic cell vaccine on patients with chronic hepatitis B: A clinical study

AIM: To investigate the therapeutic effect of autologous HBsAg-loaded dendritic cells (DCs) on patients with chronic hepatitis B. METHODS: Monocytes were isolated from fresh peripheral blood of 19 chronic HBV-infected patients by Ficoil-Hypaque density gradient centrifugation and cultured by plastic-adherence methods. DCs were induced and proliferated in the culture medium with recombinant human granulocyte-macrophage-colony- stimulating factor (rhGM-CSF) and human interleukin-4 (rhIL-4). DCs pulsed with HBsAg for twelve hours were injected into patients subcutaneously twice at intervals of two weeks. Two patients received 100 mg oral lamivudine daily for 12 mo at the same time. HBV-DNA and viral markers in sera of patients were tested every two months. RESULTS: By the end of 2003, 11 of 19 (57.9%) patients had a clinical response to DC-treatment. HBeAg of 10 (52.6%) patients became negative, and the copies of HBV-DNA decreased 101.77±2.39 averagely (t = 3.13, P<0.01). Two cases co-treated with DCs and lamivudine had a complete clinical response. There were no significant differences in the efficient rate between the cases with ALT level lower than 2xULN and those with ALT level higher than 2xULN before treatment (X2 = 0.0026). CONCLUSION: Autologous DC-vaccine induced in vitro can effectively suppress HBV replication, reduce the virus load in sera, eliminate HBeAg and promote HBeAg/anti-HBe transformation. Not only the patients with high serum ALT levels but also those with normal ALT levels can respond to DC vaccine treatment, and the treatment combining DCs with lamivudine can eliminate viruses more effectively.

Four-year follow up of hepatitis C patients vaccinated against hepatitis B virus

AIM: Patients with chronic hepatitis C have been recommended to receive vaccinations against hepatitis B. Our study aimed at evaluating the hepatitis B immunogenicity and efficacy against hepatitis B virus infection 4 years after primary immunization series in a group of patients with chronic hepatitis C.METHODS: We recruited 36 out of 48 hepatitis C virus (HCV) infected individuals who were vaccinated against hepatitis B virus (20 μg of recombinant HBsAg at 0-1-6mo schedule) in 1998. Here we measured anti-HBs titers and anti-HBc 4 years after delivery of the third dose of primary immunization series.RESULTS: After 4 years a total of 13/36 (36%) HCV infected patients had seroprotective titers of anti-HBs compared with 9/10 (90%) in the control group, (P＜0.05).Similarly the mean concentration of anti-HBs found in hepatitis C patients was significantly lower than that found in healthy subjects (18.3 and 156.0 mIU/mL respectively (P＜0.05). None of the HCV infected patients or controls became infected with HBV during the study period as confirmed by anti-HBc negativity.CONCLUSION: We demonstrated that 4 years after HBV immunizations' more than 60% of vaccinated HCV patients did not maintain seroprotective levels of anti-HBs, which might put them at risk of clinically significant breakthrough infections. Further follow-up studies are required to clarify whether memory B and T lymphocytes can provideprotection in chronic hepatitis C patients in the absence or inadequate titers of anti-HBs.

Impact of Hepatits B Vaccination as an Important Indicator for Immunization Program in Albania

Albania has been a country with a high prevalence of hepatitis B virus. Hepatitis B vaccine has been introduced nationwide in Albanian Immunization Program in 1994. Hepatitis B is given at birth, as a separate antigen, followed by three doses at 2, 4 and 6 months, where Hepatitis B, starting from 2009, is part of pentavalent vaccine of DTP-HepB-Hib. The aim of this study was to evaluate Immunization Program with Hepatitis B vaccination in order to prove program efficacy, increase public confidence in immunizations and advocate for sustainable immunization programs. Methodology was based on three components such as Immunization coverage surveys, serologic surveys and surveillance for acute cases of Hepatitis B. Results of this study showed that vaccination coverage is really high, more than 95% all over the country and with drop-out rates less than 10%. Anti-HBs levels in immunized children were very high in comparison with unimmunized ones. Incidence of HBV in children 0-14 years old is almost zero. Such results tell us that Hepatitis B vaccination is one of the most fruitful strategies for long term control of Hepatitis B disease.

The Experimental Study on Treating Transgenic HBV Mice with Recombined IL-2-PreS DNA Vaccine

The aim of this study is to investigate the feasibility and mechanism of hIL-2-preS DNA vaccine as prevention and therapeutic approach against Hepatitis B. Eukaryon expression vector involving hIL-2 and preS gene was constructed with recombinant technique and transferred into normal BALB/c mice and HBV transgenic mice (Tg-Mice) respectively. Then a series of detection were performed: detection of anti-preS2, HBs antibody and HBsAg in BALB/c mice and Tg-mice with ELISA, quantification of HBV DNA copies in HBV Tg-mice serum with real-time PCR, determination of hepatitis degree with immunopathological HE staining and detection of liver function. Anti-preS1 can be detected at 4 th , 6 th and 10 th week in inoculated BALB/c mice. Injection with gene gun gained an advantage over muscular and subcutaneous injection since it acquired just 1/10 inoculation quantity (10 μg/mouse). Highest expression of IgG2a at 4 th week suggested Th1-mediated immune response, which facilitated HBV cleaning. Of all inoculated HBV Tg-mice, 80% of them showed anti-preS2, HBs antibody positive and HBV DNA decreased, and 20% showed negative for HBsAg. HE staining to hepatic tissue showed obvious infiltration of inflammatory cells, swelling and granular degeneration of hepatocytes. In our study, IL-2-preS DNA vaccine which can provoke the humoral and cellular immune response and break the immune tolerance supports the designation and construction of new vaccine against HBV and specific immune remedy for HBV continuous infection.