Immunogenicity of low doses of hepatitis B vaccine in children: a study in 650 New Zealand children

Six hundred and fifty New Zealand children from 2-12 years of age were vaccinated three times with 2 mcg intramuscular (IM) doses of Merck Sharp and Dohme plasma-derived hepatitis B vaccine (H-B-Vax), at 0, 1, and 6 months, and tested 2-3 months later for antibody to hepatitis B surface antigen (anti-HBs) by radioimmunoassay (RIA). Overall, 96.5% of the children seroconverted for anti-HBs by RIA, having levels greater than 2.1 RIA S/N units, with 91.2% having values greater than 10 S/N units. Anti-HBs levels were also determined by enzyme immunoassay (EIA), by which method a significantly better response was demonstrated in 2-4-year-olds than in older children. This study demonstrated that a satisfactory anti-HBs response was obtained using one-fifth of the recommended doses of hepatitis B vaccine.     

Safety and immunogenicity of a recombinant hepatitis B vaccine

A hepatitis B vaccine produced in yeast by recombinant DNA technology was evaluated using 5-micrograms and 10-micrograms doses in a randomized trial lasting 7 months in 110 male armed forces recruits aged 17-19 years. Results were compared to those of an identical trial of a plasma-derived vaccine. No allergic reactions were observed, and the rate of mild side effects was similar to the plasma-derived vaccine. Seroconversion rates in the first month were 60% (33/55) and 67% (37/55) with the 5-micrograms and 10-micrograms doses of the recombinant vaccine, respectively. All participants seroconverted by 3 months, and none lost antibody. These results are very similar to those for plasma-derived vaccine. Comparison of titres of antibody to hepatitis B surface antigen (anti-HBs) showed a slightly higher level with the 10-micrograms than with the 5-micrograms dose of the recombinant vaccine. Geometric mean titres of anti-HBs after the booster dose were similar in the 5-micrograms and 10-micrograms dose recombinant vaccine groups (2,620 and 2,748 IU/l, respectively) and in the 5-micrograms plasma-derived vaccine group (3,591 IU/l) but significantly higher (9,227 IU/l) with the 10-micrograms dose of the plasma-derived vaccine. These results confirm the safety and immunogenicity of the recombinant vaccine, although further study is needed on the duration of immunity.     

国产重组酵母乙型肝炎疫苗人体免疫效果观察

目的我国重组酵母乙肝疫苗于１９９５年开始生产，目前对国产重组酵母乙肝疫苗的母婴传播阻断保护率和抗体应答水平尚不完全清楚。本次研究目的为评价国产重组酵母疫苗的安全性和免疫效果。方法应用３批国产重组酵母乙肝疫苗（卫生部北京生物制品研究所生产）。１批Ｍｅｒ－ｃｋ和１批Ａｍｇｅｎ进口重组酵母乙肝疫苗，对１８９名ＨＢｓＡｇ、ＨＢｅＡｇ双阳性母亲所生的新生儿进行了１年母婴传播阻断研究；同时对３６３名小学生进行了１年的免疫效果观察。免疫程序均为０，１，６月３针免疫。结果所有接种的新生儿和小学生中未发现严重副反应者。国产重组酵母疫苗母婴传播阻断保护率为８５．９７％，达到进口Ｍｅｒｃｋ（９０．３３％）和Ａｍｇｅｎ（８６．５９％）重组酵母疫苗的保护率水平。小学生完成３针免疫后１月（Ｔ７）时，接种各疫苗组的抗体阳转率均达９０％以上。结论本次研究证明国产重组酵母疫苗具有较好的安全性和近期保护效果     

Kinetics of antibody response to hepatitis B virus determinants and to recombinant vaccines in Italy.

The kinetics of antibody response to the group determinant a and subdeterminants d and y of hepatitis B virus were studied after infection and following immunisation with two recombinant DNA yeast-derived hepatitis B vaccines. The initial antibody response was to the subdeterminant epitopes, whereas anti-a antibody, which provides protection against different subtypes of the virus, was not detected for some weeks or months. The delay in the development of anti-a antibody after active immunisation raises important issues of early protection against infection.     

Comparison of safety and immunogenicity of adw and ayw hepatitis b vaccines

The safety and immunogenicity of adw and ayw hepatitis B vaccines were compared in a double-blind randomized trial in Greek Air Force recruits. One hundred and ten out of 240 eligible nonimmune recruits were randomly selected and allocated to thc two vaccine treatment groups. Two 20-m?g doses 1 month apart and a third 20-m?g booster dose, at 6 months, were given intramuscularly. Severe local or general side effects were not observed. The frequency of mild side effects (local discomfort or pain, fever less than 37.5°C, and malaise) was slightly higher with the adw than with the ayw vaccine. Antibodies developed earlier and in higher titers in adw vaccinees. However, after the booster dose all ayw and all but one adw vaccinees developed anti-HBs in almost similar titers. It is concluded that both vaccines are equally safe and immunogenic after administration of two doses at a 1-month interval followed by a booster dose at 6 months.     

乙型肝炎病毒基因疫苗诱导小鼠产生特异免疫应答

构建编码乙型肝炎病毒（ＨＢＶ）表面蛋白Ｓ的重组质粒ｐＣＲ３．１－Ｓ。将之直接肌肉注射Ｂａｌｂ／ｃ小鼠,观察小鼠ＨＢＶ特异的免疫应答。以ＥＬＩＳＡ法检测小鼠血清,＾３Ｈ－ＴｄＲ掺入法测定淋巴细胞增殖,＾５１Ｃｒ４ｈ释放法检测淋巴细胞杀伤功能。结果表明,与空载体对照组相比较,基因疫苗诱发小鼠产生良了的抗ＨＢｓ反应及ＨＢＶ特异的细胞免疫应答（Ｐ〈０．０５）,提示基因疫苗ｐＣＲ３．１－Ｓ有可能成为控制ＨＢ     

Recombinant-yeast-derived hepatitis B vaccine in healthy adults: safety and two-year immunogenicity of early investigative lots of vaccine

We tested the safety and long-term immunogenicity of two of the early investigative lots of a recombinant-yeast-derived hepatitis B vaccine in immunocompetent adults. Three 10-micrograms doses of recombinant hepatitis B vaccine (Merck Sharp & Dohme Research Laboratories, West Point, PA) were administered by deltoid intramuscular injection at time 0, 1, and 6 months to 65 seronegative adult health workers. Following a complete three-injection course, 98% of vaccinees acquired anti-HBs, 97% at levels greater than 10 mlU/ml, and 95% maintained such "protective" antibody levels at 1 year. At 2 years, 93% retained antibody, but only 68% had levels greater than 10 mlU/ml. In those who responded to vaccination by achieving any detectable level of antibody, the peak geometric mean titer of anti-HBs, measured at 9 months, was 741 +/- 6 mlU/ml; the geometric mean titer fell to 348 +/- 6 at 1 year and to 66 +/- 7 at 2 years. Side effects were trivial, and levels of yeast antibody, as measured by radioimmunoassay, were not changed from prevaccine levels. No serious adverse effects were encountered, and neither type B nor non-B hepatitis occurred in any vaccine. These findings demonstrate that the recombinant yeast hepatitis B vaccine is safe and immunogenic but that 10 micrograms of the early investigative lots of the recombinant vaccine is less immunogenic than 20 micrograms of the plasma-derived vaccine. Recipients of early investigative vaccine lots should be considered for booster vaccination with currently available, more immunogenic vaccine lots.     

国产流行性感冒病毒疫苗免疫原性研究的meta分析

目的 评价国产流行性感冒(简称流感)病毒疫苗的免疫原性.方法 通过文献检索搜集2012年9月前发表的有关国产与进口流感病毒疫苗免疫原性比较研究的文献,利用Stata10.0软件进行meta分析.结果 共有20篇符合标准的文献纳入本研究.结果显示:国产流感病毒疫苗B型抗体阳转率显著高于进口流感病毒疫苗(P=0.036,RR=1.036,95％ CI:1.002～1.070),未发现国产流感病毒疫苗3个亚型的保护率及H1N1和H3N2抗体阳转率与进口流感病毒疫苗存在显著差异(P＞0.05).进一步的亚组分析发现:国产流感全病毒灭活疫苗B型抗体阳转率(P=0.024,RR=1.040,95％CI:1.005～ 1.077)及保护率(P=0.031,RR =1.059,95％CI:1.005～1.116)、H3N2抗体(P=0.019,RR=1.053,95％ CI:1.009 ～1.098)保护率均显著高于进口流感病毒疫苗.结论 国产流感病毒疫苗具有较好的免疫原性.     

Protective efficacy, immunotherapeutic potential, and safety of hepatitis B vaccines

Hepatitis B vaccines are highly effective and safe and have been incorporated into national immunization programs in over 150 countries. The major humoral immune response is to the common a determinant of the surface antigen protein of the virus. Approximately 5-10% of healthy immunocompetent subjects do not mount an antibody response (anti-HBs). Non-response is associated with different HLA-DR alleles and impaired Th cell response, among other factors such as route of injection, age, gender, body mass, and other factors. Important hepatitis B surface antigen variants have also been identified, which may have a potential impact on immunization and routine screening of blood, blood products and tissues, and organs for transplantation. Strategies for hepatitis B immunization are reviewed. Over 1,000 million doses of hepatitis B vaccine have been used with an outstanding record of safety. There is no evidence of an association between hepatitis B vaccines and the sudden infant death syndrome, chronic fatigue syndrome, and multiple sclerosis (MS). Several studies are in progress on treatment of chronic hepatitis B infection by immunization with multiple antigenic components, combination of vaccine with antiviral drugs and cytokines, T cell vaccines, DNA vaccines alone or with DNA encoded immunomodulatory cytokines, and direct genetic manipulation of antigen presenting cells.     

Comparison of a triple antigen and a single antigen recombinant vaccine for adult hepatitis B vaccination.

Hepatitis B and its sequelae are a major public health problem. Vaccines have been available for almost 20 years; however the disease still remains a global problem. Many factors contribute to the failure to control hepatitis B, including the limited nature of the vaccination programs implemented initially. Only relatively recently has mass childhood vaccination begun to be implemented and vaccination of high-risk groups, other than healthcare workers, is still not general policy. Additional factors contributing to continued persistence of hepatitis B in the developed world are that the present vaccines are not fully used by those recommended to be vaccinated and even when vaccination is carried out appropriately, there remain some who fail to achieve adequate protection. Clearly, the protection of at-risk groups who have inadequate response to current vaccines, and those who are unwilling or unable to comply with protracted multi-dose vaccine regimens, could be improved if there were a more potent vaccine and/or a shorter vaccination regimen available. Adults who had never been vaccinated against hepatitis B were randomised to receive a vaccination course of either a present single antigen (S) vaccine (Recombivax-HB) or a novel triple antigen (S, pre-S1, and pre-S2) recombinant vaccine (Hepacare Medeva Pharma plc). Doses were given at baseline and 1 month and 6 months later. Hepatitis B surface antibody (anti-HBs) levels were measured at 2, 4, 6, and 7 months after beginning vaccination. The primary efficacy parameter was the degree of protection, measured as the percentage of subjects with anti-HBs titres > or = 10 IU/L, 6 or 7 months (26 +/- 2 weeks) after beginning vaccination. A total of 303 adult subjects entered the study and were vaccinated. Of these, 11 failed to complete the study (4 on Hepacare and 7 on Recombivax-HB); however all but 2 (1 to receive the triple antigen vaccine and 1 to receive Recombivax-HB) were included in the intent-to-treat population for efficacy evaluation. Treatment randomisation was stratified at entry based on age (above and below 40 years old) and gender. The standard three-dose/6-month vaccination regimen of the single antigen vaccine protected 83% of subjects by 7 months after starting vaccination whereas the triple antigen vaccine as a two-dose/1-month regimen protected 88% within 6 months and as a three-dose/6-month regimen protected 97% by 7 months after starting vaccination. Thus the protection rate provided by the shortened (0, 1) regimen of the novel vaccine was "essentially equivalent" (i.e., not statistically inferior) to that provided by the full (0, 1, and 6) regimen of today's vaccine (88% vs. 81%, P < 0.001), and the protection rate provided by a three-dose/6-month (0, 1, and 6) regimen of the new vaccine was significantly superior to that provided by present vaccines (97% vs. 83% P < 0.001). The percentage of subjects protected increases with time after beginning vaccination and at all time points up to and including 6 months was significantly greater with the two-dose regimen of the triple antigen vaccine than with the single antigen vaccine regimen. In adults at risk for a reduced response to hepatitis B vaccination [i.e., older adults (>/=40), the obese, males, and smokers], the triple antigen vaccine produced a significantly greater percentage of protected subjects (P < 0.001) and higher geometric mean titre (P < 0.001). Indeed as a three-dose/6 month regimen, the triple antigen vaccine raised the level of protection in these vulnerable subgroups to that seen when a single antigen vaccine is used in the optimal younger adult group. Both vaccines were well tolerated and had similar safety profiles. The most frequently (> or = 10%) reported adverse events with the use of either vaccine were pain at the site of injection (38% vs. 41% vs. 20% for the two-dose Hepacare regimen, the three-dose Hepacare regimen, and the three-dose Recombivax-HB regimen, respectively), infections at the site of injection (1% vs. 14% vs. 9%), headache (9% vs. 13% vs. 11%), and nausea (7% vs. 11% vs. 3%). It is concluded that in healthy normal adults, a triple antigen hepatitis B vaccine that contained S and pre-S antigens produced an enhanced immunological response. This was exemplified by the novel vaccine's ability to overcome factors such as advancing age (> or = 40 years), obesity, and smoking, each of which is known to reduce the potential for protection with present recombinant S only vaccines. A two-dose/1-month (0 and 1) regimen of this triple antigen vaccine was as effective as the standard three-dose/6 month (0, 1, and 6) regimen of present single antigen vaccines. (c) 2001 Wiley-Liss, Inc.     

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.     

不同剂量乙型肝炎疫苗对慢性乙型肝炎患者特异性T淋巴细胞应答反应的影响

目的研究接受不同剂量重组酵母乙型肝炎疫苗治疗的慢乙肝患者外周血淋巴细胞对疫苗的特异性细胞免疫反应。方法选择72例6个月内无使用抗病毒治疗的慢性乙型肝炎患者按1：1：1的比例随机分为90tLg组、60tLg组、安慰剂组（0μg）。患者同时联合使用干扰素alb5MIU每周3次共24周。所有患者均停药后观察24周。在不同的时间点检测患者HBVDNA、HBeAg及肝功能，酶联免疫斑点试验（ELISPOT）法检测产生IFN-7的细胞数。结果治疗前三组患者的ELISPOT阳性率的差异无统计学意义。治疗24周时高剂量、低剂量和安慰剂组ELISPOT试验阳性的患者分别有12例、12例和7例。重组酵母乙型肝炎疫苗组（高剂量、低剂量）ELISPOT阳性率比安慰剂组明显升高，差异有统计学意义（P=0．0446）。24例ELISPOT阳性的重组酵母乙型肝炎疫苗组（高剂量、低剂量）患者中有6例产生HBVDNA转阴、7例发生HBeAg消失或转换，而7例ELISPOT阳性的安慰剂组患者均无HBVDNA转阴及HBeAg消失或转换。停药后24周，ELISPOT阳性者中。重组酵母乙型肝炎疫苗组（高剂量、低剂量）共有4例产生HBVDNA转阴、9例发生HBeAg消失或转换，而接受安慰剂治疗组均无HBVDNA转阴、仅有1例发生HBeAg转换。结论重组酵母乙型肝炎疫苗对慢性乙型肝炎患者有提高特异性T淋巴细胞功能的作用。高剂量组和低剂量组ELISPOT阳性率差异无统计学意义。     

Subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection

To assess the feasibility of jet injection for mass immunization against hepatitis B virus, inactivated, alum-adsorbed hepatitis B vaccine (Merck, Sharp, and Dohme Research Laboratories, West Point, PA) was administered subcutaneously by automatic jet injection to 19 volunteers lacking antibody to hepatitis B surface antigen (anti-HBs). Three 20-μg doses were given at 0, 1, and 6 months. Of 19 volunteers, 5 (26%) developed anti-HBs by 1 month after the first injection, and 15 of 19 (79%) were anti-HBs-positive 6 to 8 weeks after the first booster administration. Following the second booster, 16 of 19 (84%) recipients had detectable anti-HBs. Possible systemic reactions were limited to low-grade fever (37.8°C) in one volunteer following one injection, and mild lethargy in a second recipient. Local reactions to jet injection of vaccine occurred more frequently, with indurated, nodular lesions 3–10 mm in diameter developing at the site of 19 of 57 (33%) vaccine injections, compared with 2 of 57 (3%) saline placebo injections. Such nodules were generally painless. Sore arms were noted in 11 of 57 (19%) vaccine injections. With the exception of frequent but minor local reactions, subcutaneous administration of inactivated hepatitis B vaccine by automatic jet injection is safe, and results in vaccine immunogenicity approximating that associated with intramuscular needle injection.     

State of hepatitis B virus DNA in leucocytes of hepatitis B patients

Hepatitis B virus (HBV) DNA in leucocytes from 50 hepatitis patients with various patterns of HBV serological markers and serum HBV DNA and 13 normal controls were examined by Southern blot hybridization with 32P-labeled 3.2 Kb HBV DNA. A free form of HBV DNA was observed in leucocytes of 8 patients, 7 of whom were positive for serum HBeAg, and in 6 patients an integrated form of HBV DNA was identified. HBV DNA was not identified in leucocytes from 13 normal controls. The free form of HBV DNA in leucocytes existed as a heterogeneous smear from 2.0 to 3.2 Kb, similar to the pattern in liver and hepatocellular carcinoma cells but different from serum HBV DNA in which the 3.2 Kb band was absent. The banding pattern of the integrated form of HBV DNA in leucocytes varied among different patients. During preparation of white blood cells and purification of HBV DNA probes, it was important to remove plasma contamination and traces of pBR322, respectively. The presence of extrachromosomal DNA sequences partially homologous to pBR322 could cause false results. The presence of a free and integrated form of HBV DNA in leucocytes is important for explaining the biology of HBV, the harbouring and replication sites of extrahepatic origin, the mechanism of recurrent infection, and the rationale of the treatment of hepatitis B.     

Reduced doses of hepatitis B immune globulin in the prevention of perinatal transmission of hepatitis B

From October 1982 to May 1983, newborn infants of 79 hepatitis B surface antigen (HBsAg)-positive women were enrolled in a study of the efficacy of hepatitis B immune globulin (HBIG) in the prophylaxis of perinatal transmission of hepatitis B virus (HBV) infection. HBIG 0.5 ml or 0.25 ml was given to the newborn within 15 minutes of birth and at 3 and 6 months. The mother-infant pairs were followed-up every 3 months for at least 9 months. Similar observations of untreated infants were used for comparison. Among infants of hepatitis B e antigen (HBeAg)-positive carrier mothers, the HBsAg carrier rates at 3 months were similar in the 0.5-ml and 0.25-ml HBIG dose groups. At 12 months the difference--17.7% of 17, 40% of 15--did not reach statistical significance, but the differences between these rates and that of the untreated control-85.7% of 35--did. Among infants of HBeAg-negative carrier mothers, HBV infection rates in both dose groups were similar to those of untreated infants. In the treated groups at 12 months about 45% of infants of HBeAg-positive mothers and 90% of infants of HBeAg-negative mothers were still negative for HBsAg and anti-HBs. Vaccination to induce active antibody is necessary to prevent postnatal infection and chronic carriage of HBV. To reduce the cost of combined passive and active hepatitis B immunoprophylaxis in children born to HBeAg-positive carrier mothers, 0.25 ml of HBIG could be used instead of the usually recommended 0.5 ml.     

比较α-干扰素不同联合治疗方案对儿童HBeAg阳性慢性乙型肝炎的疗效

目的评估两种不同的α-干扰素联合治疗对儿童HBeAg阳性慢性乙型肝炎的临床疗效。方法选择HBeAg阳性慢性乙型肝炎儿童120例,随机分为3组,每组各40例:第1组(A组)为α-干扰素(IFN-α)组;第2组(B组)为IFN-α 拉米夫定(LAM)组。第3组(C组)为α-干扰素(IFN-α) 乙肝疫苗组。其中干扰素疗程6个月,拉米夫定疗程6个月,所有病例均观察至12个月。结果治疗结束时丙氨酸转氨酶(ALT)复常率3组无差异。治疗6个月和12个月时B组HBeAg阴转率和HBV DNA的阴转率明显高于A组和B组,差异有统计学意义(P<0.05)。结论α-干扰素与拉米夫定联合治疗对HBeAg阳性慢性乙型肝炎儿童的病毒学应答(VR)疗效明显优于单用α-干扰素组和α-干扰素 乙肝疫苗组。     

Challenges related to the immunogenicity of parenteral recombinant proteins: Underlying mechanisms and new approaches to overcome it

Immune response elicited by therapeutic proteins is an important safety and efficacy issue for regulatory agencies, drug manufacturers, clinicians, and patients. Administration of therapeutic proteins can potentially induce the production of anti-drug antibodies or cell-mediated immune responses. At first, it was speculated that the immunogenicity is related to the non-human origin of these proteins. Later on, it was confirmed that the human proteins may also show immunogenicity. In this review article, we will focus on a number of factors, which play crucial roles in the human protein immunogenicity. These factors are related to the patient's status (or intrinsic properties) and molecular characteristics of the therapeutic protein's (or extrinsic properties). Furthermore, we will discuss available in silico, in vitro, and in vivo methods for the prediction of sequences, which may generate an immune response following parenteral administration of these proteins. In summary, nowadays, it is possible for drug manufacturers to evaluate the risk of immunogenicity of therapeutic proteins and implement a management plan to overcome the problems prior to proceeding to human clinical trials.     

Quantitation of hepatitis B viral DNA by solution hybridization: Comparison with DNA polymerase and hepatitis B e antigen during antiviral therapy

Serological markers of hepatitis B virus (HBV) replication were assessed in a randomized, controlled trial of prednisone withdrawal followed by α -interferon in the treatment of chronic hepatitis B. HBV DNA levels in more than 700 serial serum samples from 41 patients were determined by a sensitive and quantitative solution hybridization assay. Results were compared with HBV DNA polymerase (DNAp) activity and hepatitis B e antigen (HBeAg) in 21 untreated controls and 20 treated patients. Among treated patients, the mean pretherapy HBV DNA values were higher in nonresponders than in responders. During prednisone treatment, DNA levels increased an average of 2.1-fold in responders and 1.4-fold in nonresponders. During the 2-week rest interval between prednisone and interferon, DNA values fell an average of 57% in responders. In contrast, the mean DNA values in nonresponders did not change during the same interval. This early distinction between responders and nonresponders was not apparent from DNAp or HBeAg results. During interferon treatment, HBV DNA became undetectable in responders and remained negative during a 1-year follow-up. DNA in nonresponders declined to 14% of baseline during interferon treatment but increased to pretherapy levels after treatment. DNAp values generally paralleled HBV DNA values, but DNAp activity showed more variability and lower sensitivity than did the hybridization assay results. HBeAg values varied independently of HBV DNA and DNAp with a much delayed decline in responders. These results indicate that HBV DNA, when measured quantitatively by a sensitive solution hybridization assay, is an early predictor of the effects of antiviral agents on replication.     

Quantitative assessment of hepatitis B virus DNA in chronic hepatitis B: comparison of two solution hybridization assays

We compared two solution hybridization assays, the AffiProbe assay (Orion Corporation) and the Abbott HBV-DNA assay (Abbott), for quantitative measurement of hepatitis B virus (HBV) DNA in serum samples obtained from chronic hepatitis B surface antigen (HBsAg) carriers. Forty transversally collected (group 1) and 83 serially collected (group 2) serum samples from chronic hepatitis B patients were tested with both assays. The serial serum samples were obtained from 6 patients who underwent α-interferon therapy with different outcomes (nonresponse, hepatitis B e antigen [HBeAg] seroconversion, HBeAg and HBsAg seroconversion). In group 1 a good correlation (r = 0.91; P < 0.001) was found between the HBV-DNA results of the two assays. Two samples (5%) were HBV-DNA positive according to the Abbott but negative according to the AffiProbe assay; for all other samples the HBV-DNA status corresponded. In group 2 the assays gave colinear HBV-DNA results during follow-up of 5 of the 6 patients (correlation for the total group: r = 0.90; P < 0.001). Nevertheless, in both groups the AffiProbe assay yielded about 5–10 times higher HBV-DNA levels than the Abbott HBV-DNA assay (P < 0.001). These discordant results were most probably due to standardization differences of the positive control samples of the two test systems. This observation underlines the need for international standardization of HBV-DNA and uniform reference panels. © 1993 Wiley-Liss, Inc.     

基因工程乙型肝炎疫苗免疫原性和免疫效果的评价

80年代第一个基因工程疫苗———乙肝疫苗研制成功 ,以后随着对目的基因选择、抗原表达系统、质量评价等方面的研究进展 ,对其质量问题产生了不同见解。不同乙肝疫苗抗原来源于不同的表达系统 ,糖基化程度和生产工艺有所不同 ,由此引起保护率、抗体水平和免疫持久性的差异如何 ?以及以何种方法评价方能较科学地反映疫苗质量 ,均为乙肝预防工作中亟待解决的重大问题。开展这方面的研究 ,对确定我国乙肝疫苗生产发展的方向 ,即选择、推广何种类型的乙肝疫苗十分重要 ,为制定疫苗更新换代的行政决策提供依据。本文对疫苗免疫效果考核和保护机制…