Long-term persistence of anti-HBs after vaccination with a recombinant DNA yeast-derived hepatitis B vaccine: 8-year results

The aim of this study was to evaluate the persistence of antibodies 7 years after hepatitis B booster administration in healthy adult volunteers who were vaccinated in 1986. In October 1986, 188 seronegative, healthy adult volunteers (117 men and 71 women) were vaccinated with a 20 micrograms dose recombinant DNA yeast-derived hepatitis B vaccine. Mean age of the study group was 23.3 years (+/- 0.28). Immunisation was carried out according to a 0-1-2 month vaccination schedule, with a booster dose at 12 months. Of the 159 subjects who received the full vaccination course, 63 (40%) had a blood sample taken 8 years after the first vaccination. Of these 63 subjects, five were excluded from the analysis due to an irregular vaccination schedule and four subjects did not complete the accompanying questionnaire on possible booster administration. So, 54 subjects remained available for further analysis. Fourteen individuals had received an additional booster of hepatitis B vaccine sometime between 1989 and 1994. The geometric mean titre (GMT) at month 13 for these 14 individuals was 1494 mIU ml-1, compared with 3103 mIU ml-1 for those who did not receive an interim booster. Forty subjects, who received no additional booster dose besides that of month 12, met the inclusion criteria of the follow-up study. Of these, all subjects except one were seropositive for anti-HBs at month 96 (GMT: 215.9 mIU ml-1). All subjects were still anti-HBc negative at that time. Distribution of individual antibody titres revealed that overall 92.5% of subjects retained protective antibody levels (> or = 10 mIU ml-1); 72.5% of vaccinees retained high levels of anti-HBs (> or = 100 mIU ml-1) as compared to 99.2 and 97.0% at month 13, respectively. A positive correlation was found between the subjects' titres at month 13 and month 96. A 0-1-2 dose vaccination course with a booster dose administered at month 12, induces a protective immune response which lasts at least until 7 years after the full vaccination course of the subjects. A positive correlation was found between the anti-HBs antibody titres at month 13 and month 96.     

High immunogenicity and good tolerability of a new hepatitis A vaccine candidate

Immunogenicity and tolerability of a new formalin-inactivated, alum-adjuvanted whole virus vaccine against hepatitis A (VAQTA, MSD, West Point, USA) were evaluated by immunizing 52 healthy, anti-HAV negative volunteers with a 1 ml dose. A booster dose was given 6 months later. In these young adult vaccinees [27 males and 25 females, 19-34 (mean 26) years of age] VAQTA proved to be well tolerated and highly immunogenic. Two weeks after administration of one vaccine dose, all but one of the recipients (98%) had anti-HAV concentrations above the presumed minimum protective level of 10 IU l-1 with a geometric mean concentration (GMC) of 165 IU l-1. After 4 weeks, a 100% seroconversion rate could be demonstrated with a fourfold increase of the GMC to 728 IU l-1. Six months after vaccination, all but one of the 50 volunteers coming back for booster (98%) showed anti-HAV levels within the protective range. The antibody concentrations had decreased in the majority of vaccinees to a GMC of 362 IU l-1. The booster dose given at that time was shown to be very effective, leading to a pronounced rise of anti-HAV levels in all recipients with a 17-fold increase of the GMC to 6040 IU l-1. Six months after the booster, all vaccinees were still seropositive with a GMC of 3444 IU l-1. Higher antibody levels were found in females, the difference being significant 4 weeks and 6 months after vaccination and 4 weeks after booster. No serious local or systemic adverse reactions were observed.     

Comparison of immunogenicity of vaccination and serovaccination against hepatitis B virus in patients with alcoholic cirrhosis

OBJECTIVES: The association of anti-HBs immunoglobulins and anti-HBV vaccine could increase the immunogenicity of the latter. The aim of this prospective randomized trial was to compare the immunogenicity of anti-HBs vaccination and serovaccination in alcoholic patients with cirrhosis. METHODS: Alcoholic patients with cirrhosis were randomized in 2 groups: a) Vaccination group: 3 i.m. injections of GenHevac B followed by one booster at month 9; b) Serovaccination group: same vaccination schedule followed by one i.m. injection of anti-HBs immunoglobulins (500 IU). RESULTS: Twenty-five patients (17 males and 8 females, mean age 56 years) were included in the study: 13 received a vaccination and 12 received a serovaccination. After 12 months, the seroconversion rates were 69% and 67% in vaccination and in serovaccination groups, respectively. The predictive factors of non responsiveness were as following: Child B cirrhosis, low number of CD8, a high CD4/CD8 rate, the existence of HLA DR7 antigen, and the absence of HLA DR1 antigen. CONCLUSION: In alcoholic patients with cirrhosis, serovaccination does not increase the immunogenicity of anti-HBs vaccination and should not be recommended.     

Influence of high titers of maternal antibody on the serologic response of infants to diphtheria vaccination at three, five and twelve months of age

Diphtheria antitoxin was determined in serum from 44 pregnant women, of whom 26 had received one injection of diphtheria toxoid during pregnancy. Their infants were vaccinated with a combined diphtheria-tetanus vaccine at 3, 5 and 12 months of age. This vaccination schedule has been used in Sweden since 1986, replacing the old schedule of vaccination at 3, 4.5 and 6 months of age originally designed for diphtheria-tetanus-pertussis vaccine, which had not been used after cessation of general vaccination against pertussis in 1979. Serum samples from the infants were obtained at 3, 7 and 18 months of age. After 2 injections infants of mothers with high antitoxin titers, > or = 0.1 IU/ml, tended to have lower antitoxin titers than infants of mothers with low antitoxin concentrations (P = 0.067). All children had, however, antitoxin above the minimum protective level of 0.01 IU/ml. Median antitoxin titers were 1.6 IU/ml in both groups after the third booster injection. Four infants of mothers who had been vaccinated during pregnancy and who had titers of > or = 0.4 IU/ml did not reach the 0.1 IU/ml level after 2 injections: all 4 responded with high antitoxin titers after the third dose. Thus all infants were primed by 2 doses of vaccine, irrespective of maternal antibody concentration. The repressive effect of maternal antibody on titers noted after 2 doses was no longer observed after the third, booster dose.     

Persistence of antibodies in children after intradermal or intramuscular administration of preexposure primary and booster immunizations with purified Vero cell rabies vaccine

BACKGROUND: The use of intradermal (i.d.) injections of purified Vero cell rabies vaccine (PVRV) for preexposure prophylaxis has not been well-established. We studied the safety and immunogenicity of i.d. and intramuscular (i.m.) PVRV injections for primary and booster preexposure immunizations. METHODS: One of two rabies preexposure PVRV regimens comprising three doses of either 0.1 ml i.d. or 0.5 ml i.m. administered during 28 days was assigned at random to 190 school children. One booster dose was given 1 year later either i.d. or i.m., according to their initial randomization group. Serologic results were available from 155 (82%) children at 1 year after primary immunization and 118 (62%) children at 2 years after booster. RESULTS: Although children vaccinated i.d. had significantly lower rabies-neutralizing antibody titers after primary immunization as well as after booster than children vaccinated i.m. (P< 0.001 for all time points), there were no significant differences in the percentages of children with adequate titers (> or =0.15 IU/ml) between the i.d. and i.m. groups after both primary and booster immunizations. Mild local reactions were more frequent after i.d. vaccination. Mild or moderate systemic reactions were infrequent and similar after i.d. and i.m. vaccinations. Fever and headache were reported by < or =6%. The reactions after booster were not different from those of post-primary immunization. CONCLUSIONS: Purified Vero cell rabies vaccine appears to be safe and immunogenic for primary and booster preexposure immunizations. An i.d. PVRV preexposure regimen should be useful especially for rabies-endemic countries with low per capita income.     

Three-week hepatitis B vaccination provides protective immunity

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 micrograms each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A (n = 44): two doses at day 0, one dose at day 21; or schedule B (n = 45): one dose at days 0, 10 and 21. Seroprotection rates (anti-HBs > or = 10 mIU ml-1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A (p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.     

Evolutional neurologic evaluation of seven year-old children born prematurely

Personnel (1856 subjects) belonging to local health units (medical and paramedical staff) that have been vaccinated since 1984 against hepatitis B virus (HBV) with HBsAg plasma purified preparations (Hevac-B and H-B-Vax) or recombinant DNA preparation (Engerix-B) were followed in plasma anti-HBs antibody levels. At the end of the protocols, different seroconversion percentages and different anti-HBs levels were reached: the best results were obtained with Engerix-B. Sex and principally age influenced the antibody production: women generally reached highest protective antibody levels and the 21-30 year group was more responsive than other groups. The injection of a supplementary 4th or 5th dose in low or non-responders could restore the specific immunity in the majority of the subjects and increase the anti-HBs level. The time course after the immunization of antibody levels depended on the level reached at the end of vaccination schedule. These data suggest that different antibody level monitorings of vaccinated subjects, planned on the basis of the antibody level reached at the end of vaccination, could prevent a loss of protection against the HBV infection.     

Hepatitis B component does not interfere with the immune response to diphtheria, tetanus and whole-cell Bordetella pertussis components of a quadrivalent (DTPw-HB) vaccine: a controlled trial in healthy infants

The aim of this single-blind, parallel trial was to assess whether the hepatitis B (HB) component of a DTPw-HB vaccine interferes with the immune response to the other three components when administered at 3, 5 and 7 months of age. One hundred and six infants were randomized to receive three doses of DTPw or DTPw-HB vaccines. Seroprotection (or seroresponse) rates and geometric mean titers (GMT) of antibodies were assessed 3-6 weeks after the third dose. Anti-diphtheria, anti-tetanus and anti-Bordetella pertussis antibodies were measured by ELISA and anti-HBs by radioimmunoassay. Local and general signs and symptoms were recorded for a 4-day follow-up period after each vaccination. After the full vaccination course all subjects in both groups had seroprotective titers (> or = 0.1 IU ml-1) against diphtheria and tetanus and seroresponded (titers > or = 15 EL.U ml-1) to B. pertussis, and there was no significant difference between groups in relation to GMT. All subjects vaccinated with DTPw-HB had seroprotective levels (> or = 10 mIU ml-1) of anti-HBs antibodies after the third dose (GMT of 2318 mIU ml-1). Overall there were no significant differences between groups in relation to the incidence of local and general symptoms. These results show that the HB component did not interfere with the immune response to the other three components of the vaccine.     

Assessment of the immunogenicity and reactogenicity of a quadrivalent diphtheria, tetanus, acellular pertussis and hepatitis B (DTPa-HBV) vaccine administered in a single injection with Haemophilus influenzae type b conjugate vaccine, to infants at 2, 4 and 6 months of age

This double-blind, randomised study was performed to assess the immunogenicity and reactogenicity of three lots of a quadrivalent diphtheria-tetanus-acellular pertussis-hepatitis B vaccine (DTPa-HBV) co-administered with three lots of Haemophilus influenzae type b conjugate (Hib) vaccine in one injection, as a primary vaccination course in healthy infants at 2, 4 and 6 months of age. 269 infants (8-11 weeks of age) were randomly allocated to three groups to receive DTPa-HBV/Hib vaccines, concomitantly with oral polio vaccine. Blood samples for antibody determinations were taken before vaccination and 1 month after the third dose in 262 subjects. Local and general symptoms were recorded by parents on diary cards. All vaccinees had post-vaccination protective anti-D and anti-T (> or = 0.1 IU ml-1) antibodies, and 98% had protective anti-HBs antibody titres (> or = 10 mIU ml-1). There were no statistically significant differences between groups in post-vaccination anti-D, anti-T, anti-HBs antibody geometric mean titres (GMT), these being 3.49 IU ml-1, 5.92 IU ml-1 and 1109 mIU ml-1, respectively. All subjects responded to three pertussis components, i.e. pertussis toxin (PT), filamentous haemagglutinin (FHA) and pertactin (PRN). Although statistically significant differences in GMTs of anti-PT, anti-FHA and anti-PRN were found between groups, these were not believed to be of any clinical relevance as the minimum GMTs were 60, 193 and 230 EL.U ml-1 for anti-PT, anti-FHA and anti-PRN, respectively. There were no statistically significant differences in anti-PRP antibody GMT (4.05 micrograms ml-1) between groups, 100% and 85% of subjects having titres > or = 0.15 and 1.0 microgram ml-1, respectively. No symptoms were reported for one third of the subjects. Fever (> 38 degrees C) was reported after 16% of doses, with < 1% having > 39.5 degrees C. Almost all local and general symptoms were mild or moderate, and lasted less than 48 h. No subject dropped out due to a severe adverse reaction. The administration of an experimental mix of DTPa-HBV and Hib vaccines in a single injection is safe, well-tolerated and immunogenic for all vaccine components.     

Juvenile offenders and hepatitis B: risk, vaccine uptake and vaccination status

OBJECTIVE: To determine the hepatitis B vaccination status of juvenile offenders in a custodial setting, their perceived risk of hepatitis B infection, and factors influencing vaccine uptake. DESIGN: 130 males aged 14-17 years resident at the Melbourne Juvenile Justice Centre for at least one week between mid-January and mid-December 1996 were invited to participate; 90 (69%) completed a doctor-administered questionnaire, and blood for serological testing was obtained from 83 of these participants. MAIN OUTCOME MEASURES: Whether hepatitis B vaccine had been offered; whether hepatitis B vaccine had been given; the presence of antibodies to hepatitis B and C; risk factors and self-perceived risk of hepatitis B. RESULTS: About a quarter of participants (22/83) had protective levels of antibody to hepatitis B surface antigen (anti-HBs). Forty (44%) participants reported having been offered hepatitis B vaccine; they were more likely to be vaccinated and have protective levels of anti-HBs. Perceived risk for bloodborne virus infection was low, although two-thirds of participants were at high risk of hepatitis B infection. On serological testing, 6.4% (5/78) were positive for antibody to hepatitis B core antigen (anti-HBc), and a further 2.6% (2) had equivocal antibody levels. Of the 71 who were negative for anti-HBc, 51 (71.8%) were negative for anti-HBs. CONCLUSIONS: The targeted hepatitis B vaccination program has not adequately protected this group at high lifetime risk of hepatitis B. Failure to deliver vaccine may reflect lack of contact with healthcare services, oversight in offering vaccine and reluctance of youth to participate in preventive healthcare measures, often through not seeing themselves to be at risk. Universal approaches to vaccination may be more successful in vaccinating this group.     

The comparative study of the macular light threshold in the normal and low visual acuity people]

Hepatitis B recombinant vaccine immunoresponsiveness was studied in 427 preadolescents vaccinated with a 0, 1 and 6 months vaccination schedule. AntiHBs postvaccination titres (measured one month after the last dose) were related to the following variables: sex; weight; height; and Quetelet index. The antiHBs postvaccination titres were used to predict the length of protection induced by the vaccine. All preadolescents developed antiHBs titres 10 IU l-1 and no statistically significant differences could be found between sexes. The relation study between antiHBs postvaccination levels and Quetelet index showed a statistically significant inverse correlation. According to the antiHBs postvaccination titres, the central 50% of the sample distribution would be protected during a period between 7.5 and 10.5 years. In pre-teenagers, the hepatitis B recombinant vaccine has proven to be highly immunogenic, obesity is a predictor of poor immunoresponse and this response is not influenced by sex. According to our results, we would propose the administration of a single booster dose 10 years after primary vaccination and thus protect these subjects during the period of greatest risk.     

Divergence between biochemical and cytogenetic differences in three species of the Callicebus moloch group

Four viruses were compared for their ability to induce an intestinal antibody response in piglets. Antibodies were not detected in response to oral vaccination with either fowlpox virus or a baculovirus (BV). Simultaneous oral dosing and parenteral inoculation with high concentrations of BV in an oil emulsion adjuvant induced high levels of circulating virus neutralising (VN) antibodies, and also low levels of intestinal antibodies when booster doses of virus were given. In response to oral vaccination with swinepox virus (SPV), low levels of circulating and intestinal VN antibodies, and higher titres of antibodies reactive in an enzyme immunoassay, including intestinal antibodies of the IgA class, were detected. Oral vaccination with porcine adenovirus type 3 (PAV-3) stimulated both circulating and intestinal VN antibodies, and IgA antibodies were demonstrated in the intestinal contents. It was concluded that SPV and PAV-3 might be suitable vectors for the expression of genes encoding the protective antigens of porcine enteric viruses.     

Free and total insulin-like growth factors and insulin-like growth factor binding proteins during 14 days of growth hormone administration in healthy adults

The objective was to investigate the effect of growth hormone (GH) administration on circulating levels of free insulin-like growth factors (IGFs) in healthy adults. Eight healthy male subjects were given placebo and two doses of GH (3 and 6 IU/m2 per day) for 14 days in a double-blind crossover study. Fasting blood samples were obtained every second day. Free IGF-I and IGF-II were determined by ultrafiltration of serum. Total IGF-I and IGF-II were measured after acid-ethanol extraction. In addition, GH, insulin, IGF binding protein 1 (IGFBP-1) and IGFBP-3 were measured. Serum-free and total IGF-I increased in a dose-dependent manner during the 14 days of GH administration. After 14 days, serum-free IGF-I values were 610 +/- 100 ng/l (mean +/- SEM) (placebo), 2760 +/- 190 ng/l (3 IU/ m2) and 3720 +/- 240 ng/l (6 IU/m2) (p = 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.004 for 3 IU/m2 vs 6 IU/m2). Total IGF-I values were 190 +/- 10 micrograms/l (placebo), 525 +/- 10 (3 IU/m2), and 655 +/- 40 micrograms/l (6 IU/m2) (p < 0.0001 for 3 and 6 IU/m2 vs placebo; p = 0.04 for 3 IU/m2). There were no differences in the levels of free or total IGF-II during the three study periods. Insulin-like growth factor binding protein 1 was decreased during GH administration (p = 0.04 for placebo vs 3 IU/m2; p = 0.006 for placebo vs 6 IU/m2). In conclusion, fasting serum free IGF-I increased dose dependently during GH administration and free IGF-I increased relatively more than total IGF-I. This may partly be due to the decrease in IGFBP-1.     

Atelectasis of the maxillary sinus. Analysis of progression stages. Apropos of 4 cases

Evaluation of the diphtheria protection in 764 healthy volunteers before and after the vaccination showed that 56.3% had a reliable immunity, 22.8% a doubtful and 20.9% had no immunity. A high risk is in the age group 41-50 years. Young medical personal and alcoholics also have insufficient diphtheria immunity. The results of 41 healthy volunteers with a basic immunisation of more than 10 years ago prove that one booster shot is sufficient irrespective of the moment of the last vaccination.     

Immunogenicity of an inactivated hepatitis A vaccine in Dutch United Nations troops

Limited information existed on the immunogenicity of an inactivated hepatitis A vaccine as part of an extensive vaccination schedule. Dutch marines bound for duty in Cambodia received inactivated hepatitis A vaccine (720 ELISA units of antigen, two intra-gluteal doses at a 2-week interval before departure and an intra-deltoid booster vaccination after 8 months) simultaneously with several other vaccines. Hepatitis A antibodies were determined in blood-samples drawn before and after the booster vaccination, using two laboratory tests (modified HAVAB and SBB-ELISA). At 8 months, before the booster vaccination, 52% (modified HAVAB) and 81% (SBB-ELISA) had seroconverted. Risk factors for non-seroconversion were increasing age and a typhoid vaccination. At 11 months 97.6% (modified HAVAB) and 100% (SBB-ELISA) had seroconverted. Non-seroconversion at 8 months was remarkably high. SBB-ELISA was more sensitive in lower titre ranges.     

Immunity status against poliomyelitis in persons 13-14 years old living in Rome

The immunity against poliomyelitis in 1000 subjects 13-14 years old was evaluated. Neutralizing antibodies against poliovirus type 1, 2 and 3 were detected in 97.6%, 95.8% and 70% of samples, respectively. 3/1000 (0.3%) subjects were simultaneously seronegative to the three types. WHO does not suggest a protective level of International Units (IU), but our data indicate that such level is 0.45 IU for polio type 1, 0.65 IU for the type 2 and 0.138 for the type 3. A booster dose of vaccine in adolescence to ensure personal and herd immunity is recommended.     

Safety and immunogenicity of a combined diphtheria-tetanus-acellular pertussis-inactivated polio vaccine-Haemophilus influenzae type b vaccine administered at 2-4-6-13 or 3-5-12 months of age

METHODS: In an open randomized study we compared the safety and immunogenicity of two schedules for priming and booster vaccinations of infants. A pentavalent combination vaccine, including a lyophilized Haemophilus influenzae type b-tetanus toxoid conjugate vaccine reconstituted with a liquid diphtheria, tetanus, acellular pertussis (pertussis toxoid and filamentous hemagglutinin) and inactivated polio vaccine (DTaP-IPV/Act-HIB; Pasteur Mérieux Connaught, Lyon, France) was administered to 236 Swedish infants either at 2, 4 and 6 months or at 3 and 5 months, and a booster dose was administered 7 months after the last primary dose. Adverse events were monitored by diaries for 3 days after each vaccination and by questions at the ensuing visits. Antibodies against the different vaccine components were analyzed after the primary series of vaccinations, before and after the booster injections. RESULTS: There were no serious adverse reactions, and the rates of febrile events and local reactions were low in both groups. The three dose primary schedule induced higher geometricmean concentrations for all antigens than did the two dose schedule, but there were no differences between the groups in proportions with protective antibody titers against diphtheria, tetanus, Hib and polio or in proportions with certain defined levels of pertussis antibodies. Prebooster results showed a similar pattern, with the exception that the group primed with three injections showed higher proportions of infants with detectable antibodies against polio-virus types 1 and 3. After booster vaccinations there were no differences between the two schedules in geometric mean or in proportions with antibodies above defined antibody concentrations, indicating effective priming from both primary series of vaccinations. Conclusion. The combined vaccine DTaP-IPV/ Act-HIB vaccine was equally safe and immunogenic when administered according to both time schedules studied.     

Revised cutoff values of serum aminotransferase in detecting viral hepatitis among CAPD patients: experience from Taiwan, an endemic area for hepatitis B

BACKGROUND: To determine the best cutoff values of aspartate aminotransferase (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C infection among patients of continuous ambulatory peritoneal dialysis (CAPD). METHODS: 90 (44 male and 46 female) CAPD patients and 526 adult controls (266 male, 260 female) were enrolled. Serum AST and ALT were measured by an auto-analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an second-generation EIA method. The best cutoff values of AST and ALT for detecting viral hepatitis were obtained from the ROC (receiver-operating characteristic) curve. RESULTS: The prevalence of anti-HCV(+) was significantly higher in CAPD patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was similar in both groups. CAPD patients had significantly lower levels of serum aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients with HCV infection had higher serum AST and ALT levels than those without. However, HBV infection did not cause significant serum aminotransferase elevation in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l) for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2% respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial aminotransferase values, the sensitivity of AST and ALT for detecting HCV were 36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly revised criteria. CONCLUSIONS: Serum aminotransferase cutoff values should be modified for screening viral hepatitis in a CAPD population. Our new cutoff criteria had important clinical implications in providing benefits of earlier detection and possible prevention from chronic hepatic deteriorations.     

Adverse reactions after diphtheria-tetanus booster in 10-year-old schoolchildren in relation to the type of vaccine given for the primary vaccination

This prospective open study investigated adverse reactions in 527 schoolchildren to a diphtheria-tetanus (DT) booster given within a national vaccination programme at 10 years of age. Evaluation was based on those whose immunization records showed that they had received either three doses of an adsorbed DT vaccine (n = 388) or a non-adsorbed DT-pertussis vaccine (DTP) (n = 69) for primary series vaccination. No differences in systemic reactions to the booster between the two groups were observed. Local reactions were significantly (p < 0.001) more common 1 day after vaccination in children who had received DT for primary series vaccination: redness, 73% compared with 23%; swelling, 56% versus 15%; and itching, 47% versus 21%. One and 2 weeks after the booster, itching was still more pronounced in the group who had received DT for primary series vaccination (p < 0.001 and 0.014, respectively). The study indicates that there was a real basis for the increase in spontaneous notifications of local side-effects to the school DT booster in Sweden. The most likely cause for the increase seems to be the aluminium adjuvant in the vaccine given for primary vaccination, a late and unexpected consequence of a change in the infant immunization programme.     

Occlusion of the femoral artery induced fos-like immunoreactive neurons in the lateral habenular nucleus projecting to the midbrain periaqueductal gray in the rat

BACKGROUND: Inactivated hepatitis A vaccines are licensed with a vaccination schedule based on two injections of vaccine given at least 6 months apart. METHODS: Two vaccination schedules for the inactivated hepatitis A vaccine, AvaximTM (Pasteur Mérieux Connaught, Lyon, France), were compared in a monocentric, randomized, open trial. Two doses of the vaccine were given at intervals of either 6 months (0-6 month group) or 12 months (0-12 month group) to 96 adult volunteers. Anti-hepatitis A virus (HAV) antibody titers were determined in a blind fashion using the modified RIA (mRIA) HAVABtrade mark assay. After excluding subjects with positive preimmunization anti-HAV titers and those with protocol deviations, both groups were still comparable by sex ratio and mean age. RESULTS: Four weeks (28 6 4 days) after the first dose, the seroconversion (SC) rate of initially HAV-seronegative subjects (antibody titer < 20 mIU/mL) was 100% in the 0-6 month group and 96. 9% in the 0-12 month group, with corresponding geometric mean titer (GMT) values (95% CI) of 369 mIU/mL (274-497 mIU/mL) and 445 mIU/mL (292-679 mIU/mL), respectively. After 6 months, SC was obtained in all subjects, and the corresponding GMT values were 349 mIU/mL and 359 mIU/mL in the 0-6 month group and the 0-12 month group, respectively. Four weeks after the booster dose given at 6 months, a 14.5-fold rise in GMT was observed. In the 0-12 month group, anti-HAV GMT values decreased by only 20% from 6 months to 12 months with a pre-booster GMT value of 286 mIU/mL at the 12-month evaluation. Four weeks after the booster given at 12 months, a 22. 5-fold rise in GMT was observed. Statistical analysis showed that the two vaccination schedules were comparable in their ability to boost antibody titers. Unsolicited reactions to vaccination were not different to those reported during earlier trials. Less than 12% of the vaccinees reported reactions after the first dose (11/93), or after the booster dose (11/92). CONCLUSIONS: This trial demonstrated antibody persistence is excellent for at least 12 months after one dose of this vaccine, and that a booster may be given at any time between 6 and 12 months after primary immunization.