乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗免疫效果的比较

目的：比较乙型肝炎卡介苗联合疫苗与单价乙型肝炎疫苗的免疫效果。方法：实验动物采用豚鼠，按0、1、2月三针免疫程序接种，并于每针免疫后1个月采血，ELISA方法检测血清抗体滴度。实验分三部分进行。实验一：三种不同规格的联合疫苗与单价乙型肝炎疫苗的比较；实验二：同一规格连续三批联合疫苗与单价乙型肝炎疫苗的比较；实验三：联合疫苗与两种单价疫苗同时免疫的比较。结果：在三个实验中，联合疫苗组第一针血清抗体滴度均低于对照组，但无统计学差异：联合疫苗组第二、三针血清抗体滴度均高于对照组，也无统计学差异，实验组各组之间无明显差异。结论：联合疫苗组三针免疫程序的HBsAg的效力与单价乙型肝炎疫苗组相似。     

Clinical and immunological investigation of a new combined hepatitis A and hepatitis B vaccine

As with hepatitis B vaccines, the recently developed hepatitis A vaccine is suitable not only for individual protection, but also for public health control measures. For introduction into routine immunisation programmes, however, hepatitis A vaccine should preferably be combined with other already established vaccines. In particular, a combination of hepatitis A and hepatitis B vaccines would be appropriate. We investigated a new combined hepatitis A/hepatitis B vaccine comparing its tolerability and immunogenicity with that obtained after separate or mixed simultaneous administration of the two components. Three groups of healthy volunteers, each of approximately 50 persons, were included. All were negative for hepatitis A and hepatitis B markers and had normal liver enzyme values. They received hepatitis A (720 ELISA units) and hepatitis B (20 m?g) vaccines in the deltoid muscle, combined, mixed or separately, according to a 0, 1, 6-month schedule. Blood samples for determination of antibodies to hepatitis A virus (anti-HAV) and hepatitis B virus (anti-HBs) and of serum ala-nine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were drawn at months 0, 1, 2, 6, and 7. Local and systemic reactions were monitored by means of questionnaires. The results of our study demonstrate that the combined hepatitis A and B vaccine is well tolerated and highly immunogenic. The seropositivity and seroprotection rates were 100% for both antigens in all groups. Surprisingly, anti-HAV and anti-HBs antibody titres after the combined and mixed vaccines were significantly higher compared with the respective monovalent vaccines injected separately. © 1994 Wiley-Liss, Inc.     

Immunogenicity of a five-microgram dose of hepatitis B vaccine

The immunogenicity of a 5-μg dose of vaccine (H-B-Vax, MSD) was evaluated in 50 young adults (17–19 years). Results were compared to our previous studies using similarly prepared vaccines using 20 μg and 10 μg per dose with the same trial protocol in a comparable population. Seroconversion rates for the 5-μg doses of vaccine were 80% after the first dose and 98% after the second dose. The remaining participants did not develop anti-HBs in the course of the trial. These results are not significantly different from those observed in the 10-μg and 20-μg studies. The increase of anti-HBs titers was slower for the 5-μg group. High geometric mean titers were observed after booster vaccination, but lower for the 5μg (3,591 mIU/ml) than for 10 μg (9,277 mIU/ml) and 20 μg (12,975mIU/ml) doses. It is concluded that 5-μg dose of the vaccine is effectively immunogenic for young adults.     

CpG ODN联合乙型肝炎疫苗与乙型肝炎疫苗免疫效果对比研究

目的探讨CpG ODN乙型肝炎疫苗与市售乙型肝炎疫苗对Balb/c小鼠的免疫作用效果。方法将乙肝疫苗、乙肝疫苗+100μgCpG ODN分别肌肉注射到4～6周龄,16～18g Balb/c小鼠体内,于第1次免疫后28d以同样剂量加强免疫1次。分别于第1次免疫后28、42、63 d收集小鼠血清,用ELISA方法检测抗HBs IgG抗体。结果实验组产生的抗HBs IgG与对照组HBsIgG相比P<0.05,具有显著性差异。28、42、63 d抗HBs IgG分别是对照疫苗的114倍、4.73倍、5.41倍以上。结论 CpG ODN能够显著增强小鼠对乙肝疫苗的免疫应答,在较短时间内显著的提高乙肝抗体的产生水平,免疫效果是乙肝疫苗的5倍以上。     

Bivalent inactivated hepatitis A and recombinant hepatitis B vaccine

Hepatitis A and B remain serious global public health problems. Monovalent vaccines against hepatitis A and B have been available for many years. Since 1996, licenses have been gradually introduced for different formulations and immunization schedules of the first combined vaccines against both diseases. Twinrix Adult (with conventional and accelerated schedules) is available for the immunization of individuals aged 16 years or older in Europe and 18 years or older the USA. Twinrix Pediatric, with its three-dose schedule, and AmBirix, with its two-dose schedule, are licensed in Europe for ages 1-15 years. These vaccines offer a single injection for satisfactory protection against hepatitis A and B and an excellent safety and reactogenicity profile in comparison with monovalent vaccines. This article focuses on immunogenicity of the vaccines and proposes expert opinion and future directions in this field.     

Evaluation of a reduced dose of hepatitis B vaccine administered intradermally

Intradermal inoculation of hepatitis B vaccine (HBsAg subtype adw) caused no side effects, but the vaccine was less immunogenic than following intramuscular administration. Intradermal inoculation does not, therefore, offer a major advantage to the generally used intramuscular immunization. A single multisite intradermal administration of a reduced dose of vaccine did not result in a more rapid seroconversion compared to intramuscular inoculation. Although the antibody levels were similar after two intradermal or intradermal or intramuscular injections given 1 month apart, the booster (third injection) at 6 months resulted in anti-HBs levels that were about 10 times higher following intramuscular inoculation as compared to intradermal. All persons immunized developed anti-HBs. The levels of anti-HBs (a and w) were about 30-40% of the total anti-HBs, and the proportion did not change significantly during the course of immunization. Cross-protection against all HBV strains is thus also assured after intradermal administration of vaccine containing only one HBsAg subtype (adw). A skin reaction was elicited only in a small proportion of anti-HBs-positive individuals, and the reaction correlated roughly with the immune responses.     

Immunogenicity and protective efficacy of low dose recombinant DNA hepatitis B vaccine in normal and high-risk neonates.

A low dose of recombinant DNA hepatitis B vaccine (HB-VAX II, MSD) was tested for efficacy in the prevention of perinatal hepatitis B virus (HBV) transmission in normal and high-risk neonates born from HBsAg carrier mothers. A dose of 2.5 micrograms recombinant vaccine was injected intramuscularly at 0, 1, 2 and 12 months of age to 30 newborns from HBsAg negative mother (group I), 30 from HBeAg negative/HBsAg carrier mother (group II) and 30 from HBeAg positive/HBsAg carrier mother (group III). The incidence of persistent HBsAg carrier infants at 13 months of age was 0, 0, and 30.4 percent in groups I, II and III, respectively. The protective efficacy in high risk infants in group III was 65.7 percent. The seroconversion at month 4, after the third dose of vaccination was 96.3, 95.7 and 100 percent in group I, group II and group III, respectively. After a booster dose of vaccination at 12 months of age, the seroconversion rose to 100 percent at month 13 in all three groups. The geometric mean titer (GMT) of anti-HBs antibody at 13 months of age were 2,092, 1,657 and 1,938 mIU/ml in group I, group II and group III, respectively. It is concluded that the low dose (2.5 micrograms) recombinant hepatitis B vaccine using alone is effective in prevention of perinatal HBV transmission in low risk infants (groups I and II), but it is less effective in high risk infants (group III).(ABSTRACT TRUNCATED AT 250 WORDS)     

A review of the efficacy, immunogenicity and tolerability of a combined hepatitis A and B vaccine

Hepatitis A and B are two of the most common vaccine-preventable liver diseases and continue to be a significant cause of morbidity and mortality worldwide, with their severity related to the individual's age upon initial infection. Twinrix (GlaxoSmithKline), a combined vaccine providing protection against both hepatitis A and B, has been available in more than 72 countries worldwide since 1997. This paper provides a critical review of clinical data on the efficacy, immunogenicity and tolerability of the combined vaccine, with particular focus on the clinical benefits of dual vaccination.     

Immunogenicity of a low dose recombinant DNA hepatitis B vaccine in healthy adults in Singapore

The immunogenicity and safety of a standard dose of 10 micrograms of a yeast derived recombinant DNA hepatitis B vaccine (B-Hepavac II) was compared with that of a reduced dose of 5 micrograms in 84 healthy adult volunteers with no previous exposure to hepatitis B. Each subject received either a 10 micrograms or 5 micrograms dose of vaccine intramuscularly at 0, 1 and 6 months. One month after the second injection of vaccine the seroconversion rate in the two groups were 85 and 86 percent respectively. Two months after the third injection 100 percent of participants had sero-converted; 95 percent of the 10 micrograms group and 91 percent of the 5 micrograms group had titres of anti-HBs greater than 10 IU/L. The geometric mean titres (GMT) of anti-HBs levels at 2, 6, 8, and 12 months were 34, 61, 811 and 188 IU/L in the 10 micrograms group and 26, 45, 836 and 304 IU/L in the 5 micrograms group respectively. Adverse effects were mild and transient. The vaccine was safe and immunogenic in the doses given. The reduced dose of 5 micrograms was as effective as the standard 10 micrograms dose.     

乙型肝炎疫苗的研究新进展

乙型肝炎疫苗(HepB)接种是阻断乙型肝炎病毒(HBV)传播、预防乙型肝炎的最有效方法。HepB可以分为预防性疫苗和治疗性疫苗。本文综述了HepB及其佐剂的研究新进展,指出乙型肝炎治疗性疫苗以及新型疫苗佐剂是当前HepB研究的重要方向。此外,针对HepB的免疫不良反应和无(弱)应答问题提出应对措施。     

不同剂量乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果对比

目的 探讨10 μg和20 μg乙肝疫苗与HBIG联合免疫阻断HBV母婴传播的效果.方法 124例HBsAg阳性孕妇所生的婴儿随机分为两组,即10 μg乙肝疫苗组和20 μg乙肝疫苗组.婴儿于出生6h内及30 d分别注射200 IU HBIG,同时分别于出生24 h内、1个月及6个月注射3次10 μg或20 μg重组酵母乙肝疫苗.检测婴儿出生时以及1岁时血清HBV标志物.结果 两组新生儿血清HBsAg、HBeAg及抗-HBe阳性率与滴度之间差别均无统计学意义（P＞0.05）.所有新生儿血清HBV DNA水平均小于检测下限（500 U/ml）.出生12个月时,所有124例婴儿血清HBsAg和HBeAg检测结果均为阴性;血清HBV DNA水平均在检测下限以下;10 μg和20 μg乙肝疫苗组血清抗-HBs阳性率分别为90.3％和96.8％,差异无统计学意义（P＞0.05）;抗-HBs水平分别为325.5±342.2 mIU/ml和463.7±353.3 mIU/ml,后者显著高于前者（P=0.01）.而且,20 μg乙肝疫苗组产生高应答抗-HBs（＞ 100 mIU/ml）的比例显著高于10μg乙肝疫苗组（P =0.035）.结论 20 μg乙肝疫苗联合HBIG方案阻断HBV母婴传播的效果优于10 μg乙肝疫苗联合HBIG方案.     

Different HBs antibody versus lymphoproliferative responses after application of a monovalent (hepatitis B) or combined (hepatitis A + hepatitis B) vaccine

BACKGROUND: The aim of the study was to evaluate a possible adjuvanticity of simultaneous hepatitis A (HAV) vaccination for the development of HBs-specific antibodies and lymphoproliferative responses in prophylactic immunization with hepatitis B (HBV). METHODS: Thirty-nine volunteers were vaccinated (schedule: 0/1/6 months) either with a bivalent HAV/HBV (18 individuals) or with HBV (recombinant HBs-antigen) vaccine alone (21 individuals). Anti-HBs antibody titers and lymphoproliferative responses as consequence of stimulation of peripheral blood mononuclear cells (PBMC) with HBs were evaluated and compared between the two groups before second vaccination, before and 1 month after booster. RESULTS: Geometric mean titers were higher at all time points in the group treated with the combined vaccine. On the other hand, after the booster injection, HBs-induced stimulation indices in PBMC were higher in the group vaccinated with HBs alone. Neither the difference in antibody titers nor in proliferative responses reached the level of statistical significance. Interestingly, the inverse relation between cellular proliferation and antibodies was significant, indicating that cellular reactivity is not in all cases a useful marker to evaluate the intensity of the induced immunity. CONCLUSIONS: The magnitude of the T-lymphocyte response may eventually not be decisive for the subsequent antibody response. Both vaccination strategies led to a cellular and humoral immune response and resulted in protective levels of HBs-specific antibodies.     

The immune response of healthy adults to a reduced dose of hepatitis B vaccine

Three hundred thirty-six medical personnel from hemodialysis centers were treated with three doses, 20 μg each, of the Merck hepatitis B vaccine (at 0, 1, and 6 months). Within 1 month after the first injection, 41% converted to anti-HBs positivity; after the second injection the conversion rate rose to 80–90%; and after the booster, to 96–98%. The later rate remained unchanged during the 18-month follow-up period. Only 2.8% of those vaccinated did not respond to the vaccine. The patterns of immune responses to 20-μg doses were found to be exactly the same as to 40-μg doses. It is suggested that reduced doses of vaccine should be as efficacious as the larger ones.     

新生期接种乙肝疫苗联合丰富环境对小鼠神经发生及行为的影响

目的探究新生期接种乙肝疫苗联合丰富环境对小鼠神经发生及行为的影响,为其更深入的机制研究奠定基础。方法新生小鼠均等的随机分为两组,其中半数小鼠出生24 h内腹腔注射乙肝疫苗(100μg/m L),于出生后第1、3周分别加强免疫一次,其余注射无菌PBS作对照。待出生后第4周,子代小鼠再次被均等的随机分为两组,分别为丰富环境组和普通环境组。利用水迷宫实验检测小鼠海马依赖型的学习记忆能力;免疫荧光技术检测小鼠海马的神经发生;ELISA方法检测小鼠血清中的IL-4、IFN-γ以及海马中的BDNF含量。结果乙肝疫苗联合丰富环境组小鼠的学习记忆能力、神经发生及海马的BDNF水平高于乙肝疫苗组小鼠,差异具有统计学意义(P<0.05),但与对照组小鼠相比无显著差异(P>0.05);联合组小鼠血清中的IFN-γ/IL-4比值较乙肝疫苗组小鼠明显升高,差异具有统计学意义(P<0.05),与对照组小鼠相比并无显著差异(P>0.05)。结论新生期接种乙肝疫苗损害小鼠的神经发生和海马依赖型的学习记忆能力,并使得小鼠Th1/Th2平衡向Th2偏移,青春期进行丰富环境干预后可使其恢复到与对照组相近的水平。     

Comparison of two testing methods to determine hepatitis B surface antibody response to hepatitis B vaccine among health-care workers

Because of variations in reported seroconversion rates and to compare enzyme-linked immunoassay (EIA) and radioimmunoassay (RIA) methods to assess hepatitis B vaccine response, hepatitis B surface antibody (anti-HBs) was tested in 116 of 174 high-risk hospital employees enrolled in a hepatitis B vaccine program. All individuals were vaccinated with three injections of Heptavax-B, 1.0 ml containing 20 micrograms of HBsAg intramuscularly in the deltoid. The same lot of appropriately stored vaccine was used. Of the 41 individuals tested within zero to six months postvaccination, 35 (85%) and 38 (93%) were positive by EIA and RIA, respectively. Of the 75 individuals tested 7-24 months postvaccination, 61 (81%) and 71 (95%) were positive by EIA and RIA, respectively. Results of EIA tests performed at two laboratories were similar. Of 109 individuals positive by RIA, 13 did not have protective antibody levels. In contrast, of 96 individuals positive by EIA, only one did not have a protective antibody level. RIA may be a more sensitive test for anti-HBs, but a positive EIA result correlates better with protective antibody levels.     

不同剂量配比的实验性甲型肝炎戊型肝炎联合疫苗的免疫原性研究

目的研究实验性甲型肝炎(甲肝)戊型肝炎(戊肝)联合疫苗的免疫原性,探讨两种抗原组分间的相互作用。方法制备9种不同剂量配比的实验性甲戊肝联合疫苗,与单价疫苗对照一起免疫15组(共120只)小鼠,定时采血,以ELISA和中和试验检测抗HAV和抗HEV的抗体。结果高剂量的HAV抗原(5×105U/L)与不同剂量的HEV抗原(200、100、50mg/L)配制的联合疫苗,诱导的抗HAV中和抗体的滴度可达1∶1024,含25×104、125×103U/LHAV抗原的联合疫苗诱导的中和抗体滴度为1∶512,不同剂量的HEV抗原对抗HAV中和抗体的产生均无明显影响。与单价戊肝疫苗相比较,联合疫苗诱导的抗HEV抗体水平均有明显升高,且随联合疫苗中HAV抗原的含量(5×105、25×104、125×103U/L)的增加而升高,HEV抗原的剂量在一定范围内(200、100、50mg/L)与抗HEV抗体产生无明显关系。采用基于逆转录套式PCR的中和试验表明,各联合疫苗组的免疫血清均可中和HEV。结论实验性甲、戊肝联合疫苗内HAV抗原对HEV抗原的免疫原性具有增强作用,而HEV抗原对HAV抗原的免疫原性无明显影响。