Polymeric lamellar substrate particles as carrier adjuvant for recombinant hepatitis B surface antigen vaccine

Blank polymeric lamellar substrate particles (PLSP) of poly (l-lactide) were prepared and recombinant hepatitis B surface antigen (rHBsAg) was adsorbed onto these particles. The physical characteristics of blank PLSPs or PLSP-rHBsAg in vitro and its immunological responses in Balb/c mice were investigated. The average size of the particles was less than 10 μm. Antigen adsorption efficiency was found to be 62.66 ± 1.26%. Immunization with PLSP-rHBsAg resulted in upregulation of specific cellular (lymphoproliferation, IFN-γ and NO release) as well as IgG response in animals. These responses were higher than those produced by two-dose schedule of alum-adsorbed antigen (alum-rHBsAg). Thus in conclusion, in terms of convenience and efficacy PLSP-rHBsAg is superior to alum-rHBsAg.     

Detecting hepatitis B surface antigen mutants

Hepatitis B viral mutants can emerge in patients as a result of selection pressure from either immune response or treatment options. Mutations that occur within the immunodominant epitopes of hepatitis B surface antigen (HBsAg) allow mutant virus to propagate in the presence of a neutralizing immune response, while wild-type virus is reduced to undetectable levels. HBsAg mutants present as false-negative results in some immunoassays. An understanding of immunoassay reactivity with HBsAg mutants is key to establishing an appropriate testing algorithm for hepatitis B virus detection programs.     

Influence of maternal antibody against hepatitis B surface antigen on active immune response to hepatitis B vaccine in infants

Transplacentally acquired maternal antibodies in infants may inhibit active immune responses to vaccines. In this study, we compared the immunogenicity of the recombinant hepatitis B vaccine, which was intramuscularly injected at 0, 1, and 6 months of age, in 71 infants born to mothers with positive or negative antibody against hepatitis B surface antigen (anti-HBs). Forty-one infants born to anti-HBs positive mothers were all positive at birth. At 2 months after the second injection, anti-HBs in 30 infants with negative maternal antibody was significantly higher than that in 41 infants with positive maternal anti-HBs (191.1mIU/ml vs. 96.2mIU/ml, P=0.018). At one month after the full immunization, the anti-HBs levels had no statistical difference between maternal anti-HBs negative and positive groups, but the antibody response in infants with high maternal anti-HBs (>1000mIU/ml) was significantly inhibited. Nevertheless, all infants had anti-HBs higher than the protective level. In conclusion, passively acquired maternal anti-HBs in infants may to some extent impair the antibody response to hepatitis B vaccine. The long-term efficacy of hepatitis B vaccine in infants with high titers of maternal anti-HBs remains to be further evaluated.     

在校大学生乙肝疫苗普种效果对比观察

目的 分析北京市农村居民乙肝疫苗接种状况及影响因素,为提高农村居民乙肝疫苗接种率和乙肝防控政策的制定提供参考依据。 方法 本研究数据采集于2011年1月 — 2012年4月,应用随机抽样的方法和结构式访谈问卷调查的方式在北京大兴区3个自然村进行入户调查 ≥ 16岁成年人,并采用方差分析、二元logistic回归模型进行统计分析。 结果 本研究共调查2 006人,总接种率29.86 %。其中男性1 004人（50.05 %）,接种率30.38 %,女性1 002人（49.95 %）,接种率29.34 %;平均年龄39.8岁。多因素分析中,结合回归系数和OR值分析可得,随着年龄的下降、家庭人均年收入的增加、乙肝认知水平的增加,乙肝疫苗的接种概率逐渐上升（P < 0.01）。职业分组中,接种率由高到低依次是学生、固定工作者、个体工商业者、打工者、农民（P < 0.01）。到达最近的医疗机构花费的时间越短,乙肝疫苗接种概率越高（P < 0.01）。 结论 高年龄、低收入、认知水平低都是阻碍乙肝疫苗接种的重要因素,农民和打工者群体接种率最低,医疗服务的可及性也会影响乙肝疫苗接种率。     

乙型肝炎病毒表面抗原变异的检测

HBV可因免疫或治疗的选择压力而出现变异,HBsAg变异株可在有中和抗体存在时增殖,而野毒株则会下降到不能检测的水平。HBsAg变异株在有些免疫学试验中呈假阴性,了解HBsAg变异株在免疫学试验中的反应性对建立适宜检测HBsAg的方法是很重要的。     

抗—HBs不同水平者接种乙型肝炎疫苗的初探

After hepatitis B vaccine immunization, serum antibody response was of primary type in 33 cases with anti-HBs less than 2.1 S/N (S/N Ratio Unit) at T0, the anti-HBs positive rate was 39.4%, 84.8%, 96.7% and 96.7% in T1, T2, T0 and T12 respectively. Anti-HBs S/N rose gradually month by month, the antibody response in younger children was better than that in adult. Anamnestic type in 38 cases with anti-HBs greater than 2.1 S/N at T0, the antibody levels rose rapidly in T1, T2 and began to fall in T8. The children were negative for HBsAg, anti-HBs and anti-HBc in sera by RPHA, PHA and ELISA respectively, most (100% in 1-4 age group and 63.2% in 5-9 age group) of them were also negative for HBV serological markers by SPRIA repeatedly, thus they were susceptible and need for hepatitis B vaccine immunization. Indication of hepatitis B vaccination for adult population was also discussed.     

乙型肝炎表面抗原和e抗原阳性产妇所生新生儿乙型肝炎母婴传播阻断效果的影响因素

目的探讨乙型肝炎(乙肝)表面抗原(HBsAg)和e抗原(HBeAg)阳性产妇所生新生儿在出生后乙肝疫苗(HepB)和乙肝免疫球蛋白(HBIG)联合免疫以及完成HepB全程免疫后乙肝病毒(HBV)突破性感染的影响因素。方法2016年6月-2017年5月在南昌市2个县(区)选择HBsAg和HBeAg阳性产妇所生新生儿,在联合免疫和HepB全程免疫完成后1-2个月检测血清HBsAg和乙肝表面抗体(HBsAb),分析儿童母婴传播阻断失败率(HBsAg阳性率)。结果本研究共纳入278名婴儿,母婴传播阻断失败率为2.52%(7/278),HBsAb阳性率为96.8%(269/278)。产妇HBsAg阳性时间在2年以上是阻断失败的危险因素,而分娩方式、喂养方式、母亲和婴儿HBIG的使用情况和婴儿性别等与HBV阻断失败率无相关性。结论HepB和HBIG联合免疫对HBsAg和HBeAg阳性产妇所生新生儿具有较好的乙肝母婴传播阻断效果,建议加强育龄妇女HBsAg和HBeAg筛查。     

两种方法测定乙型肝炎血清学标志物的结果分析

目的 探讨酶联免疫吸附法(ELISA)和时间分辨荧光免疫分析法(TRFIA)检测乙型肝炎表面抗体HBsAb)的结果并进行对比分析.方法 218份样本每份均用ELISA和TRFIA两种方法进行HbsAb定量和定性检测,操作步骤均严格按照《全国临床检验操作规程》和试剂盒各自附带的说明书的要求进行;并对结果进行判断分析.结果 218份标本应用TRFIA法和ELISA法检测结果比较,HBsAg、HBeAg、抗-HBe结果符合率较高均＞ 90.00％,差异无统计学意义,而抗-HBs、抗-HBc结果符合率均为88.99％,差异有统计学意义P＜0.05).结论 采用TRFIA法检测乙型肝炎血清标志物优于传统ELISA法,有利于提高乙型肝炎的诊断率,同时可以根据血清标志物表达量的改变来评估患者的病情发展及传染性的强弱;较传统ELISA法更准确、可靠,值得临床推广.     

Anamnestic response to administration of purified non-adsorbed hepatitis B surface antigen in healthy responders to hepatitis B vaccine with long-term non-protective antibody titres

A clinical trial with four groups receiving either 0.6, 3.5, 10 or 20 micro g of purified non-adsorbed hepatitis B surface antigen (HBsAg) was performed to study the kinetics as well as the capacity of the immune memory to respond following exposure to HBsAg in responders to a complete course of hepatitis B vaccine, in whom anti-HBs titres had declined below the seroprotective level. The study population included 64 healthy individuals. All response parameters seropositivity, seroprotection rates, booster response rates and geometric mean titres (GMTs), consistently showed that the immune response was highly satisfactory and dose-dependent. A remarkable immune response was obtained even with a trace amount of HBsAg. This study further supports recent indication that booster hepatitis B vaccine doses may be unnecessary in healthy adult responders to a full course of hepatitis B vaccination.     

The incidence of hepatitis B surface antigen in Nigeria

We have determined the incidence of hepatitis B surface antigen (HBsAg) in an urban (Enugu) and a rural (Okpatu) population groups in Nigeria. There were no statistically significant differences between the incidence in the two populations. Contrary to earlier reports we did not observe any significant age-related differences in the incidence rates within either population group. In general our results are similar to those reported for the urban inhabitants of Ibadan (several hundred miles west of Enugu) and its surrounding rural population. The low carrier rate recorded for schoolchildren drawn from a mainly high socio-economic group in our population has led us to suggest that socio-economic status alone or together with exposure to mosquito and other insect bites are probably the most relevant factors in the transmission of HBsAg in Nigerians.     

Hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) combine CpG oligodeoxynucletides as a novel therapeutic vaccine for chronic hepatitis B infection

Hepatitis B virus infection is a non-cytopathic hepatotropic virus which can lead to chronic liver disease and hepatocellular carcinoma. Traditional therapies fail to provide sustained control of viral replication and liver damage in most patients. As an alternative strategy, immunotherapeutic approaches have shown promising efficacy in the treatment of chronic hepatitis B patients. Here, we investigated the efficacy of a novel therapeutic vaccine formulation consisting of two HBV antigens, HBsAg and HBcAg, and CpG adjuvant. This vaccine formulation elicits forceful humoral responses directed against HBsAg/HBcAg, and promotes a Th1/Th2 balance response against HBsAg and a Th1-biased response against HBcAg in both C57BL/6 and HBV transgenic mice. Vigorous cellular immune response was also detected in HBV transgenic mice, for a significantly higher number of HBs/HBc-specific IFN-γ secreting CD4+ and CD8+ T cells was generated. Moreover, vaccinated mice elicited significantly intense in vivo CTL attack, reduced serum HBsAg level without causing liver damage in HBV transgenic mice. In summary, this study demonstrates a novel therapeutic vaccine with the potential to elicit vigorous humoral and cellular response, overcoming tolerance in HBV transgenic mice.     

Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine

We successfully re-vaccinated hepatitis B virus (HBV) vaccine non-responders using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.