Reactogenicity and immunogenicity of a new recombinant hepatitis B vaccine containing Pre S antigens: a preliminary report

SUMMARY. A new vaccine against hepatitis B virus (HBV) infection, produced in mammalian Chinese hamster ovary (CHO) cells, contains the small (s), middle (Pre S2) and large (Pre SI) surface proteins of HBV. Three injections of a 5-μg or 10-μg dose were administered intramuscularly (i.m.) at 0, 1 and 6 months to a group of 105 young adults, who were monitored for a period of 6 months after the third injection. Seroconversion rates were 100% after the second injection of the 5-μg or 10-μg dose. Geometric mean litres of HBsAb at 1 month after the third injection were 12156 mIU ml^-1 and 13 482 mIU ml^-1 in those receiving the 5-μg and 10-μg dose respectively. The vaccine was well tolerated with no significant adverse events. These preliminary results suggest that the Pre S-s recombinant vaccine, produced in mammalian cells, is highly immunogenic, leading to 100% seroconversion in the population tested after injection of only two doses of 5 μg.     

Hepatitis B third-generation vaccines: improved response and conventional vaccine non-response – third generation pre-S/S vaccines overcome non-response

A new triple-S containing recombinant hepatitis B vaccine was evaluated in terms of immunogenicity and reactogenicity in a cohort of healthy healthcare professionals who were persistent non-responders to the currently licensed hepatitis B vaccines. One hundred subjects were allocated randomly to receive two doses of 5, 10, 20 or 40 μg of a new hepatitis B vaccine 2 months apart. The overall seroconversion rate was 70% with a single dose of 20 μg of the vaccine being as effective as two doses of either 20 μg or 40 μg of the vaccine formulation in terms of seroconversion, seroprotection and geometric mean titres.     

Efficacy and safety of hepatitis B vaccination in haemodialysis patients

Antibody response to vaccination with hepatitis B vaccine was evaluated in 39 haemodialysis patients. Three injections of 20 μg of the vaccine were given at time 0, 1 and 6 months. The seroconversion rate for the antibody to hepatitis B surface antigen (anti-HBs) was 2.6% at 1 month, 15.4% at 2 months, 33.3% at 4 months, 41.0% at 6 months and 59.0% at 7 months (males 53.6%, females 72.7%). Thus, with three injections, the seroconversion rate was significantly smaller and antibody titres were lower compared with 348 healthy control subjects. No correlation was observed between the anti-HBs seroconversion rate and lymphocyte subsets (OKT4/OKT8). When two additional injections were given at 9 and 10 months to 19 haemodialysis patients with an S/N ratio (the ratio of ct/min in the sample to mean ct/min in negative controls) smaller than 10 at 7 months, 16 patients (84.2%) developed anti-HBs and elevated antibody titres. Accordingly, the response rate of all haemodialysis patients 12 months after the first injection was elevated to 92.3% and was as high as that in normal subjects. At 24 months, the response rate had gradually declined to 64.1% accompanied with lowered antibody titres. There were no serious side effects.
From these results, it was concluded that the most effective dose and schedule for optimal hepatitis B immunization and booster injections should be decided in haemodialysis patients with low antibody titres.     

Safety and immunogenicity of an inactivated thimerosal‐free influenza vaccine in infants and children

Objective Few prospective studies of inactivated split virion influenza vaccine have been conducted in infants and children. Our objective was to evaluate the safety, reactogenicity and immunogenicity of a thimerosal‐free inactivated influenza vaccine (Fluvax^®; CSL Limited, Parkville, Australia) in children aged 6 months to <9 years. Methods A prospective, open‐label, phase III clinical trial was conducted in 298 healthy children previously unvaccinated with influenza, commencing in the Southern Hemisphere 2005 autumn. Participants were divided into two groups (Group A: ≥6 months to <3 years; Group B: ≥3 years to <9 years), and received two doses of the 2005 vaccine, and one dose of the 2006 vaccine one year later (Group A: 0·25 ml per dose; Group B: 0·5 ml per dose). Vaccine safety and reactogenicity was evaluated for 30 days after each dose. Immunogenicity was assessed using hemagglutination inhibition and single radial hemolysis assays. Results There were no withdrawals due to adverse events (AEs). The majority of solicited local and systemic AEs were of mild severity. A maximum intensity of severe was reported for injection site pain and fever by only 3·0% and 3·4% of participants, respectively. The vaccine was immunogenic for all antigens, with ≥95% of both younger and older children achieving seroprotection after dose 2. Conclusions This thimerosal‐free inactivated influenza vaccine had a favorable safety profile and was immunogenic in children aged ≥6 months and <9 years. Primary and booster vaccination produced consistently immunogenic responses including in children under 3 years of age receiving 0·25 ml doses of vaccine.     

Combined passive and active immunization for interruption of perinatal transmission of hepatitis B virus in Taiwan

We attempted a clinical trial to interrupt transmission of hepatitis B virus (HBV) infection from hepatitis B surface antigen (HBsAg) positive and hepatitis Be antigen (HBsAg) positive mothers to their infants in Taiwan. Screening of 5,595 pregnant women revealed that 856 (15.3%) were HBsAg positive. Three hundred and sixty-one (42.2%) of the HBsAg positive pregnant women were HBeAg positive. Infants born to HBsAg and HBeAg positive mothers were randomized into 3 groups to receive the HBV vaccine alone or combined with hepatitis B immune globulin (HBIG). HGV vaccine was given at 2, 6, and 10 weeks after birth. Group I received HBV vaccine alone while Group II received HBV vaccine in combination with HBIG at birth and group III received HBV vaccine plus HBIG at birth and again at one month old. Group IV constituted the control group when their parents refused vaccination. At 6 months of age, the HBV carrier rate was 23.7% (9/38) in Group I, 11.1% (4/36) in Group II, and 5.3% (2/38) in Group III infants. Compared with 90% of infants who became HBV carriers in the control group (Group IV), the efficacy of HBV vaccination in preventing HBV infection among these high risk infants at the 6th month was 73.7% in Group I, 87.7% in Group II, and 94.1% in Group III. The antibody to HBsAg (anti-HBs) positivity rate in sera of Group I, II, III infants at 6 months of age was 79.0%, 88.9% and 94.7%, respectively. These initial results indicate that combined passive and active immunization is efficacious in interrupting perinatal transmission of HBV infection.     

按标准方案和加强方案接种重组乙型肝炎疫苗后AIDS病人的免疫应答

目的比较艾滋病（AIDS）病人按标准方案和加强方案接种重组乙型肝炎（乙肝）疫苗后免疫应答的差异。方法 CD＋4T淋巴细胞计数〈200个/μL、抗乙肝病毒表面抗原抗体（抗-HBs）阴性的AIDS病人89例,其中55例（A组）按标准方案分别在0、1、6个月肌内注射重组乙肝疫苗20μg,34例（B组）按加强方案分别在0、1、2、6个月肌内注射重组乙肝疫苗40μg。两组在首剂注射后1个月及7个月时检测抗-HBs滴度,≥10mIU/mL即为阳性。结果 A组在首剂注射后1个月及7个月时,抗-HBs阳转率分别为40.00%（22/55）、50.91%（28/55）,B组分别为35.29%（12/34）、67.65%（23/34）。两组在首剂注射后1个月时及7个月时,抗-HBs阳转率差异均无统计学意义（χ2=0.197、P=0.657;χ2=2.406、P=0.121）。首剂注射后7个月时,A组抗-HBs滴度的中位数为10.44mIU/mL,B组抗-HBs滴度的中位数为57.73mIU/mL,两组比较差异有统计学意义（Z=-2.018、P=0.044）。结论CD＋4T淋巴细胞计数〈200个/μL、抗-HBs阴性的AIDS病人,按加强方案接种重组乙肝疫苗后,血清抗-HBs阳转者抗-HBs滴度高于标准方案,但抗-HBs阳转率两种方案无差异。     

Hepatitis B vaccination of newborn infants: clinical study of new vaccine formulation and dose regimen

To investigate the efficacy in anti-HBsAg response with half the recommended adult dose in a standard vaccination schedule or with a full dose in reduced number of vaccination schedule, 201 healthy newborn infants were randomized to receive either 2.5 micrograms Hevac B vaccine at birth [1, 2 and 14 months in Group I (101)] or 5 micrograms at birth [2 and 14 months in Group II (100)]. Anti-HBsAg responses in the two groups were compared. Passively acquired anti-HBsAg positivity rates at birth were 51.5 and 45.0% in Groups I and II, respectively. Cumulative anti-HBsAg seroconversion rates in Group I were 12.2, 76.6, 82.6 and 86.4% at 2, 4, 14 and 16 months, while the rates in Group II were 2.5, 62.5, 73.7 and 91.0%, showing no significant difference (p greater than 0.05). Significant difference in seroconversion rates at the 2-month follow-up stage between passively acquired anti-HBsAg-negative and -positive groups was observed (11.9 vs. 2.6%). Significant rise in anti-HBsAg titer at 16 months following the booster at 14 months was noted: 36.4 mIU per ml before, 546.4 mIU per ml after in Group I and 25.3 mIU per ml before, 782.6 mIU per ml after in Group II. The booster, 12 months after the primary vaccination series, is therefore considered imperative for maximum effectiveness of hepatitis B active immunization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response to the complete hepatitis B vaccine regimen in infants under 12 months of age: a case series

ObjectivesDescribing rates of seroconversion and its associated factors in a series of Brazilian infants following the final dose of the vaccine at 6 months of age.MethodsPeripheral blood samples were collected after the third dose of the vaccine for the detection of anti-hepatitis B surface antibodies among infants of 7–12 months of age. We measured the association between seroconversion and birthweight, gestational age, time since administration of the vaccine in the maternity hospital and whether or not testing for hepatitis B surface antigen had been performed during pregnancy.ResultsWe examined 40 infants. The mean birthweight was 2787 g (standard deviation = 853 g) and mean gestational age was 37.5 (standard deviation = 3.08) weeks. The proportion that seroconverted was non-significantly higher in infants who weighed ≥2000 g at birth (96.7%) than in those with birthweights <2000 g (80%, p = 0.149). There was no difference between the infants who were born at <37 weeks of gestational age and those born at ≥37 weeks (p < 0.178) neither between seroconversion and the time of application of the first dose of the vaccine after delivery (p = 0.202).ConclusionThe proportion of infants who seroconverted was similar to that found in other Brazilian studies. There were no differences in the proportion seroconverting by age at first immunization.     

Immunogenicity of a 'pre-S2 plus S' hepatitis B vaccine in healthy adults

SUMMARY. The product of the pre-S plus S gene of hepatitis B virus appears to be more immunogenic in mice than the S-gene product (HBsAg) alone. Therefore, we tested the immunogenicity in healthy adults of a hepatitis B vaccine containing the 'middle protein' gene product of pre-S2 plus S (pre-S vaccine). We compared the immunogenicity of three doses of the pre-S vaccine with that of a commercially available recombinant hepatitis B vaccine (Recombivax-HB®): 87 seronegative adults were randomized to receive 12 μg (group 1), 24 μg (group 2), or 48 μg (group 3) of the pre-S vaccine or 10μg of Recombivax-HB (group 4) by deltoid injection at 0, 1 and 6 months. Antibody to HBsAg (anti-HBs) appeared after booster vaccination in 94% of vaccinees. Immunogenicity was best in recipients of 48 μg of the pre-S vaccine and Recombivax-HB, and geometric mean titres (GMT) for the pre-S vaccine were higher than those for Recombivax-HB only at the pre-S vaccine dose of 48 μg (group 3). Antibody to pre-S2 developed in 75% of the pre-S2 vaccine recipients (not in Recombivax-HB recipients) within 7 months. These findings indicate that the pre-S vaccine is immunogenic in healthy adults but that a dose of 48 μg of the current formulation is required to equal or exceed the immunogenicity of currently available, recombinant S-only vaccine. Studies in non-responders to S-only vaccines will be necessary to define an immunological advantage of the pre-S vaccines, and additional assessments will be necessary to determine whether anti-pre-S2 enhances protective efficacy.     

Study on the comparative immunogenicity of a recombinant DNA hepatitis B vaccine containing pre-S components of the HBV coat protein with non pre-S containing vaccines

Abstract A new recombinant hepatitis B vaccine (SCI-B-VAC), derived from Chinese hamster ovary (CHO) cells and consisting of both the major S protein and the minor pre-S₁ and pre-S₂ proteins of the viral coat were compared with two yeast-derived vaccines containing only S proteins (B-Hepavac II and Engerix-B) for immunogenicity in human volunteers in a randomized controlled study. Two hundred and ninety-five healthy subjects completed the 12 month follow up. There was no difference in the mean age and sex distribution among the three study groups. Seroconversion rates for all the three groups were similar at months 6, 9 and 12. However, hepatitis B surface antibody (anti-HBs) geometric mean titres (GMT) were significantly higher with 10 μg SCI-B-VAC and 20 μg Engerix-B than with 10 μg B-Hepavac-II at months 6, 9 and 12. SCI-B-VAC at month 6 also showed a significantly higher anti-HBs GMT than Engerix-B (295 vs 143 miu/mL, P < 0.02).     

Immune response to measles vaccine in 6 month old infants in Papua New Guinea

Objective  To assess the efficacy of the current measles immunization schedule in Papua New Guinea, which is to give the first dose at 6 months of age and the second at 9 months.
Methods  Humoral immune response study of 140 Papua New Guinean infants at 6 months of age, measuring measles IgG antibodies by enzyme immunoassay before and 85 days after the 6-month dose of measles vaccine.
Results  After vaccination at 6 months, 35.7% of infants developed a level of measles antibodies consistent with protection (IgG >330 IU/ml); 17.7% had an antibody response (150–330 IU/ml) that is likely to afford some protection; 46.8% had no detectable antibody response (IgG <150 IU/ml). Among 53 infants with no antibody response, 37 (69.5%) developed an antibody response, while 42.4% (37/87) of those with maternal antibodies sero-converted ( P  = 0.002).
Conclusions  Antibody response to measles vaccine was lower than expected at 6 months. While the presence of maternally derived antibodies accounted for some of the limited seroconversion in young infants, other factors are involved. Issues to be considered in determining the value of the first dose of measles vaccination in mid infancy in poor countries are complex and antibody responses are only one factor. Others, such as cell mediated immune responses, the non-specific protective effect of measles vaccine in preventing illness and death and the practicalities of uptake of vaccines at different ages, are also important.     

乙型肝炎病毒e抗原阳性孕妇所生婴儿联合免疫接种后乙型肝炎病毒血清学标志物的动态变化

目的 观察HBeAg阳性且HBV DNA高载量孕妇所生婴儿用乙型肝炎疫苗联合免疫接种后的母婴阻断效果及HBV血清学标志物的动态变化.方法 回顾性分析HBeAg阳性且HBVDNA≥106拷贝/ml孕妇127例,婴儿出生后即刻及第15天于臀大肌注射高效价乙型肝炎免疫球蛋白200 IU,出生时与第1、6个月于右上臂肌肉注射乙型肝炎疫苗20μg,随访其婴儿至12个月龄.用酶联免疫吸附法及荧光定量PcR检测婴儿出生时及第1、7、12个月时的HBV血清学标志物和HBV DNA载量,观察婴儿出生时HBV血清学标志物模式、母婴传播率、疫苗接种后的HBV宫内感染率、抗-HBs阳性保护率及HBV血清学标志物动态变化.结果 127例孕妇分娩婴儿均为单胎,出生时29例婴儿HBsAg为阳性,其中11例合并HBV DNA阳性,母婴垂直传播率为22.83％.随访至1个月,10例婴儿合并HBV DNA阳性从而发生HBV宫内感染,表现为HBsAg、HBeAg及抗-HBc均为阳性.2例婴儿HBsAg弱阳性,伴有抗-HBs滴度的产生,后续随访中均转阴,乙型肝炎宫内感染率为7.87％.非宫内感染婴儿出生时HBeAg及抗-HBc阳性率分别为96.58％和98.29％,免疫接种后婴儿HBeAg及抗-HBc逐步转阴,均未产生抗-Hbe.非宫内感染婴儿均产生有效乙型肝炎保护性抗体,乙型肝炎疫苗及高效价乙型肝炎免疫球蛋白联合免疫接种后,婴儿抗-HBs滴度从出生至12个月龄逐步上升,母源性HBeAg滴度逐步下降以至转阴.结论 乙型肝炎疫苗联合高效价乙型肝炎免疫球蛋白免疫接种能明显降低HBV母婴传播,增强婴儿乙型肝炎表面抗原保护性抗体,体内母源性HBeAg及抗-HBc亦随之降低甚至转阴.     

Efficacy of hepatitis B immune globulin for prevention of perinatal transmission of the hepatitis B virus carrier state: final report of a randomized double-blind, placebo-controlled trial

A randomized double-blind, placebo-controlled efficacy trial of hepatitis B immune globulin (HBIG) for prevention of the mother-to-infant transmitted HBsAg carrier state was conducted in Taiwan where the carrier rate in the general population is 15 to 20%. HBIG was given immediately after birth to infants of e antigen positive HBsAg carrier mothers, and all infants were followed for at least 15 months. Among 61 placebo recipients, the carrier rate was 92%; compared with 26% among 57 infants who received 0.5 ml HBIG at birth, 3 months, and 6 months, and 54% among 67 infants who received a single 1.0 ml dose of HBIG at birth only. Efficacy was 71 and 42%, respectively, for the two treatment schedules. The most common response of HBIG-treated infants was passive-active immunization which was 27% in the single-dose group and 61% in the three-dose group. Some of the infants who became carriers were probably infected as HBIG protection waned, and we expect that higher efficacy can be achieved by hepatitis B vaccine in conjunction with HBIG.     

Immunoprophylaxis of infection with hepatitis B virus in infants born to hepatitis B surface antigen-positive carrier mothers

Infants born to carrier mothers positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) received 5 micrograms of hepatitis B virus (HBV) vaccine on four occasions. Group 1 received vaccine only, group 2 received vaccine plus hepatitis B immune globulin (HBIG) at birth, and group 3 received vaccine plus HBIG at birth and at one month. Infants born to HBeAg-positive mothers (group 4) received a reduced dose of vaccine (2.5 micrograms) on three occasions as well as HBIG at birth. As compared with 78.4% of the control group (infants whose parents refused vaccination) who became chronic HBV carriers at the age of 14 months, the protective efficacy rate of vaccination was 75.3% in group 1,85.5% in group 2,89.7% in group 3, and 87.2% in group 4. HBV vaccine (5 micrograms) was also given to infants born to HBsAg-positive, HBeAg-negative mothers on four on four occasions. The antibody response to HBsAg in vaccine recipients was 12% after the first dose, 44% after the second dose, and 75% and 100% at six months and 1.5 years of age, respectively.     

Evaluation of a low dose of hepatitis B vaccine given within a childhood immunisation programme in Singapore

The feasibility of introducing low dose (5 micrograms) hepatitis B (HB) virus vaccination at birth and again 1 and 2 months later as part of an existing primary immunisation programme of childhood, was assessed in 662 healthy newborn Singapore children. The vaccine (B-Hepavac, Menck, Sharp and Dohme) was given to three neonatal groups: those born to HB surface antigen (sAg)-negative mothers, HBsAg-positive/HBeAg-positive mothers and HBsAg-positive/HBeAg-negative mothers. A dose of 5 micrograms was compared in a randomised study with the more usual 10 micrograms dose given at the same intervals. Neonates born to HBsAg-positive/HBeAg-positive mothers were also given hepatitis B immunoglobulin (HBIg) at birth. The 5 microgram dose of vaccine was as immunogenic as the 10 microgram dose in all three groups of children studied. At 1 year, anti-HBsAg seroconversion among infants of antigen-negative mothers was 95.8% for the 5 microgram dose and 91.9% for the 10 microgram dose. Suppression of anti-HBsAg formation was not seen even when maternal anti-HBsAg was present or HBIg given. Among infants born to HBsAg-positive/HBeAg-positive mothers, passive plus active immunisation was 100% protective at doses of 5 micrograms and 10 micrograms vaccine in the newborns who were HBsAg-negative at 24 h. Seroconversion after both the 5 and 10 microgram doses of vaccine was reduced, however, to 88% in each group of infants who were already HBsAg-positive at 24 h of age. Overall, passive plus active immunisation as well as HB vaccine alone (5 micrograms dose), given within the existing but expanded primary immunisation programme of childhood, was effective in preventing infection and the chronic carrier state in newborns exposed to risk of HB virus infection during infancy.     

Trial of Edmonston-Zagreb measles vaccine in infants aged under nine months.

Due to the recent finding that most infants in developing countries have lost maternal antibody for measles before nine months of age, immunization of infants younger than the recommended age of nine months would help reducing the incidence of measles in these endemic areas. We conducted a trial of Edmonston-Zagreb measles vaccine which is the strain that may be more immunogenic in young infants than the widely used Schwarz strain. Forty-five infants with mean age of 25 weeks received a dose of Edmonston-Zagreb vaccine. Antibody levels were measured, using plaque neutralization test, before and about 3 months after vaccination at which mean age was 38 weeks. The seroconversion rate was 89%. Only two infants (4.4%) had immunity before vaccination. Fifteen infants (33.33%) reported some adverse reactions including fever (13.33%), rhinorrhea (8.89%), rash (4.44%) and local reactions (22.22%). All of the reactions resolved spontaneously. We conclude that Edmonston-Zagreb measles vaccine is efficacious and safe in infants aged under nine months.     

Infant BCG vaccination study in Lithuania.

SETTING: Infants identified in maternity hospitals in Vilnius, Lithuania. OBJECTIVES: To test the capacity of the BCG vaccine, Danish strain 1331 (Danish vaccine), to induce tuberculin reactivity and scar formation in neonates compared to the WHO International Reference Preparation of BCG (IRP vaccine), and to study the effect of dose and of age at vaccination. DESIGN: A randomized four-armed study: 1) normal dose, 0.05 ml Danish vaccine given to neonates at birth, 2) half the normal dose of Danish vaccine given at birth, 3) IRP vaccine given at birth at normal infant dose, and 4) the normal infant dose of Danish vaccine given at 3 months of age. RESULTS: Larger tuberculin reactions, as well as an increased frequency and larger scars, were seen when Danish vaccine was given at 3 months of age in comparison to neonatal vaccination. Halving the dose resulted in smaller reactions, but the difference was not significant. The IRP vaccine resulted in borderline significantly larger reactions in comparison to the Danish vaccine. The number of infants receiving very early vaccination (0-2 days) was not evenly distributed in all groups, however, which is believed to explain the observed difference.     

Anti-HBs responses after combined injection of recombinant yeast and plasma-derived hepatitis B vaccines

Anti-HBs responses to a combined injection of recombinant yeast and plasma-derived hepatitis B vaccines were evaluated in 119 healthy members of medical staff. They were divided into three age- and sex-matched groups. Group I (YHB-YHB-YHB) were given recombinant yeast vaccine at 0, 1 and 6 months, group II (PHB-YHB-YHB) were given plasma-derived vaccine at 0 month, and then recombinant yeast vaccine at 1 and 6 months, and group III (YHB-YHB-PHB) were given recombinant yeast vaccine at 0 and 1 month and then plasma-derived vaccine at 6 months.
The seroconversion rate in each group at 7 months were similar (group I: 91.2%, group II: 88.5%, and group III: 94.1%). Acquired antibody titre (S/N ratio) was higher, however, in group II than in group I (group I: 37.6 ± 29.1 versus group II: 57.4 ± 44.9).
The present study indicated that in this combined injection method, cross antigenicity was observed between plasma-derived vaccine and recombinant yeast vaccine and that high antibody titres could be obtained by a combined injection of a recombinant yeast vaccine and a plasma-derived vaccine when compared with the recombinant vaccine alone. Accordingly, this combined vaccination method is recommended because of its easy availability.     

Granulocyte-macrophage colony-stimulating factor enhances the efficacy of hepatitis B virus vaccine in previously unvaccinated haemodialysis patients

The response to vaccination with recombinant hepatitis B virus (HBV) vaccine is poor in haemodialysis patients. A defect in the antigen-presenting cells may be responsible for this hyporesponsiveness. To overcome this and to improve the response to HBV vaccine in dialysis patients, we used granulocyte–macrophage colony-stimulating factor (GM-CSF) as a vaccine adjuvant. Fifteen consecutive patients with chronic renal failure (CRF), commenced on dialysis, were stratified to receive either 40μg HBV vaccine (Engerix-B) at 0, 1, 2 and 6 months (group A, n =9) or 3μg kg^–1 GM-CSF (Leucomax) on day 1 followed by the vaccination schedule described above (group B, n =6). All patients were negative for hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV) and human immunodeficiency virus (HIV) serology. Titres of antibody to HBsAg (HBsAb) were quantitatively assayed, using enzyme-linked immunosorbent assay (ELISA), at 1, 2, 6 and 7 months from the first dose of vaccination. Only 44% of the patients in group A developed protective antibody levels (mean HBsAb: 22 IU l^–1) Fifty per cent of responders developed protective antibody levels (HBsAb >10 IU l^–1) only after the fourth dose of vaccination. In contrast, all six patients (100%) in group B developed protective levels of HBsAb (mean HBsAb: 70 IU l^–1) ( P <0.02). Sixty-seven per cent of the responders were protected after only the second dose of vaccination ( P =0.046). No serious adverse effects of GM-CSF were observed in group B. Hence, haemodialysis patients respond poorly to HBV vaccine. GM-CSF is a safe vaccine adjuvant capable of stimulating an earlier and a stronger antibody response to HBV vaccine in haemodialysis patients.     

体内电穿孔增强日本血吸虫核酸疫苗免疫保护作用的研究

目的探讨体内电穿孔技术增强日本血吸虫核酸疫苗的免疫保护效果。方法分别大量制备质粒pcDNA3．1-SjC23、pcDNA3．1-SjCTPI、pcDNA3．1-（CDR3）6和重组蛋白SjC23-HD、SjCT-PI与NP30。上述3种质粒DNA以等量混合后即为鸡尾酒式DNA疫苗，3种蛋白以等量混合后即为鸡尾酒式蛋白疫苗。70只BALB／c小鼠随机分为A、B、C、D、E5组，每组14只。A组为自然感染组；B组（电脉冲空质粒对照组）每只小鼠分别在第0、3、6周经股四头肌注射100μl pcDNA3．1，每次注射时辅以体内电穿孔；C组（电脉冲空质粒＋混合蛋白对照组）空质粒免疫及体内电穿孔同B组，但于第9周每鼠经背部皮下多点注射100μl混合蛋白疫苗＋100μl福氏完全佐剂（FCA）；D组（电脉冲混合DNA组）每只小鼠分别在第0、3、6周经股四头肌注射100μl混合DNA疫苗，每次免疫时辅以体内电穿孔；E组（电脉冲混合DNA＋混合蛋白组）混合DNA免疫及体内电穿孔同D组，但于第9周每鼠经背部皮下多点注射100弘1混合蛋白疫苗＋100μl FCA。DNA免疫组末次免疫后4周，蛋白加强组末次免疫后2周，所有小鼠同时经腹部皮肤感染（40±1）条尾蚴。攻击感染后42d剖杀小鼠，计数成虫及肝脏虫卵数。首次免疫前2d及感染前2d分别经尾静脉采血，分离血清检测kG抗体水平、抗体亚类IgGl及IgG2a，并取小鼠脾脏制备单个脾细胞，检测细胞因子IL-2、IL-4、Ifn-y的水平。结果C、D组和E组的减虫率分别为18．09％、45．00％和57．09％，D组和E组的减虫率均显著高于C组（P均〈0．01），且E组的减虫率高于D组（P〈0．05）；C、D组和E组的减卵率分别为12．49％、50．88％和59．26％，D组和E组的减卵率均显著高于C组（P均〈0．01），且E组的减卵率高于D组（P〈0．05）。C、D、E3组小鼠血清都检测到特异性IgG抗体，抗体亚类IgG2a／IgGl比值分别为0．394、3．518、0．914。D