Follow-up immunogenicity of an inactivated hepatitis A virus vaccine in healthy children: results after 5 years

Long-term persistence of hepatitis A virus (HAV) serum antibody in vaccinated children has not been demonstrated in previous studies. To study the long-term immunogenicity to HAV vaccine, three doses of strain HM 175 HAV vaccine with 360 enzyme-linked immunosorbent assay units were administered to 107 children, aged from 1.0 to 6.8 years, at 0, 1, and 6 months. The administration of one vaccine dose induced seropositivity (anti-HAV titer > or = 20 mIU ml-1) in 95% of all vaccinees at month 1. All subjects remained seropositive until month 6. The titers of HAV antibody remained above 20 mIU ml-1 in all subjects followed up to 60 months. The geometric mean titer (GMT) reached its peak (3802 mIU ml-1) at month 7, i.e. 1 month after the booster dose, and then declined until the end of follow-up at month 60 (661 mIU ml-1). A trend of higher GMT in female subjects persisted up to month 60. The changes of the GMT over time were best described by the regression equation: log (GMT) = 3.26-0.08 x (age in years) (r = -0.95, P = 0.014). According to this equation, the geometric mean concentration would reach 20 mIU ml-1 at around 24.5 years after the beginning of vaccination. In conclusion, those who completed the recommended three-dose inactivated HAV vaccination series remained seroprotective for at least 5 years. Theoretically, such a vaccination program can provide a protective period of over 20 years in children. This paper may be the first to describe at least 5-year immunogenicity of inactivated HAV vaccination in healthy children.     

Long-term follow-up of hepatitis A vaccination in children

We conducted this follow-up study to evaluate the long-term immunogenicity of an inactivated hepatitis A vaccine in children. Ninety-six children who had seroconversion to antibody to HAV (anti-HAV) after receiving a three-dose schedule of inactivated hepatitis A vaccine were enrolled into this study. Sixty months after the initial vaccination, all vaccinees who received annual follow-up still had protective levels of anti-HAV. The geometric mean titer (GMT) of anti-HAV, peaking at month 7 (4133 mIU/mL), kept declining throughout the follow-up period. The GMTs in months 12, 24, 36, 48 and 60 were 1722, 896, 896, 645 and 403 mIU/mL, respectively. Nine of the vaccinees were hepatitis B virus carriers. Their anti-HAV titers tended to be lower than those of the remaining vaccinees at all time-points, but the difference was not significant (p > 0.05). Natural booster was noted in one vaccinee during the follow-up period. In conclusion, inactivated hepatitis A vaccine is safe and immunogenic in children, the duration of protection against HAV infection is longer than five years.     

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.     

Ogura and Powers: "Functional restitution of traumatic stenosis of the larynx and pharynx." (Laryngoscope 1964;74: 1081-1110)

The objective of this study was to evaluate the immune response and reactogenicity of a combined hepatitis B, diphtheria, tetanus and whole-cell Bordetella pertussis (DTPw-HBV) vaccine administered to healthy infants at 2, 4 and 6 months of age. A total of 179 infants (6-12 weeks of age) received three doses of DTPw-HBV vaccine. Blood samples for antibody determinations were taken before vaccination, 2 months after the second dose and 1 month after the third dose. Solicited and unsolicited symptoms were recorded by parents in a diary card. All vaccinees had protective levels of anti-HBs [geometric mean titre (GMT): 1526 mIU.ml-1], anti-diphtheria and anti-tetanus antibodies, 1 month after the third dose. Ninety-two percent of the subjects exhibited a response to the B. pertussis component. Most (99.4%) solicited reactions occurred within the first 48 h and the majority were mild or moderate. The safety, immunogenicity of this tetravalent vaccine was demonstrated when it was administered in infants following the 0, 2, 4-month dosing schedule.     

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.     

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.     

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.     

Immunogenicity and safety of a new inactivated hepatitis A vaccine: a clinical trial with comparison of administration route

A bicentre, controlled, randomized, open trial was carried out in order to compare the immunogenicity and the reactogenicity of PASTEUR MERIEUX Sérums et Vaccins inactivated Hepatitis A Vaccine on adults, when used with different routes of administration [intramuscular (i.m.), subcutaneous (s.c.) and needless injection using a Jet injector device]. Vaccines were given at two doses 6 months apart to 147 seronegative subjects. Anti-Hepatitis A virus (HAV) titres were performed at each visit by modified radioimmunoassay assay. After the first dose, 138 subjects except one seroconverted (s.c.). After booster dose, all subjects exhibited high levels of HAV antibodies. The higher titres were observed with Jet injector (GMT: 305 mIU ml-1 after the first dose and 3727 mIU ml-1 after the booster dose), followed by the i.m. route (210 mIU ml-1, 3152 mIU ml-1) and the s.c. route (165 mIU ml-1, 2082 mIU ml-1). No statistically significant differences were observed in the three paired comparisons (i.m. vs jet injector; jet vs s.c., im vs s. c.). This inactivated hepatitis A vaccine appeared to be highly immunogenic after one single dose and one booster 6 months later.     

Family practice and the advancement of medical understanding. The first 50 years

BACKGROUND: Few data exist on the persistence of measles antibodies after vaccination of West African infants. Therefore we examined measles antibody titers 5 to 7 years after children in rural Senegal had received high titer Edmonston-Zagreb (EZ-HT), high titer Schwarz (SW-HT) or standard titer Schwarz (SW-STD) measles vaccines in infancy. METHODS: Children had received either high titer vaccines at 5 months of age or standard titer at 10 months of age. Finger prick blood samples were tested for measles antibody 5 to 7 years later by the hemagglutinin inhibition test. RESULTS: Persistence of antibody after high titer vaccines was poor with the result that 39 and 50% of the EZ-HT and the SW-HT groups had low titers of hemagglutinin inhibition measles antibodies (< or =125 mIU/ml). Nineteen percent of the children in the SW-STD group had low titers which is a lower prevalence than in the high titer groups [relative risk (95% confidence intervals), 0.05 (0.28 to 0.88) vs. EZ-HT; relative risk, 0.38 (0.22 to 0.66) vs. SW-HT]. Geometric mean (95% confidence interval) antibody titers in children with detectable values were 616 (435 to 871) in the EZ-HT, 1106 (616 to 1866) in the SW-HT and 1271 (871 to 1741) mIU/ml in the SW-STD groups, respectively. Multivariant regression analysis showed that mean titers were 2.00 (1.03 to 3.89) times higher for children with low prevaccination antibody titers (< or =125 mIU/ml) and 3.06 (1.90 to 4.94) times higher if blood was collected in the rainy season. INTERPRETATION: Given the rapid decline in antibody titers over a 5- to 6-year period in an area where measles vaccine coverage was high, it seems likely that multiple dose immunization schedules will be needed in the future to maintain protective antibody concentrations (>125 mIU/ml) in West Africa. The role of subclinical boosting by exposure to natural measles and the possible role of malaria, which increases immunoglobulin turnover, in influencing long term antibody persistence after vaccination deserve further investigation.     

Fate of microinjected sperm components in the mouse oocyte and embryo

Combining HB vaccine with routine paediatric vaccines has been recognized as the best means of universal vaccination against hepatitis B. Our objective was to evaluate the long-term antibody persistence of such a combined vaccine in an area of high hepatitis B endemicity. We have shown that a DTPw-HB vaccine was safe and immunogenic when given as a booster dose at 18 months of age. One month after the booster dose of DTPw-HB vaccine, at least 97.8% of subjects had seroprotective anti-HBsAg levels, and 1 year later at least 93.9% of these subjects remained seroprotected against HBsAg. Immune responses to the DTPw components were similar or greater than those of the commercial DTPw vaccine given to the control group. This DTPw-HB vaccine, which showed good long-term anti-HBsAg antibody persistence, could advantageously replace separate DTPw and HB vaccines in areas of high hepatitis B endemicity in terms of clinical, economic and strategic benefits.     

Access to a three-dimensional measure of vertebral axial rotation

BACKGROUND: A combined diphtheria-tetanus-whole cell pertussis-hepatitis B (DTPwHB) vaccine might facilitate the achievement of universal vaccination of infants against hepatitis B. METHODS: A double blind, randomized, two-armed, single center study was undertaken to evaluate the immunogenicity and reactogenicity of combined tetravalent DTPwHB vaccine, with two dosages of hepatitis B component (10 microg and 5 microg). The combined vaccine was tested in the context of a simplified vaccination schedule at 1.5, 3.5 and 6 months of age, to 120 healthy infants born to hepatitis B surface antigen-negative mothers after priming with one dose of hepatitis B vaccine (10 microg) at birth. Antibodies to each antigenic component were measured from blood samples collected immediately after birth, pre- and postvaccination blood samples. RESULTS: The reactogenicity profiles were similar in the two groups. No serious adverse events were reported. One month after completion of the four-dose vaccination schedule, all subjects except one in Group 1 (10 microg) had protective titers of anti-HBs (10 mIU/ml). At this time the geometric mean titer in Group 1 (10 microg) was higher than that observed in Group 2 (5 microg), 696 vs. 488 mIU/ml (P = 0.19). One month after three doses all subjects in both groups had protective antidiphtheria titers and antitetanus titers. The vaccine response rate to the Bordetella pertussis component of the vaccine was 88.0% in Group 1 and 96.2% in Group 2 (P = 0.86). CONCLUSION: Both combined tetravalent vaccines are safe and immunogenic when administered to infants born to a hepatitis B surface antigen-negative mother, with a 10-microg dose of priming hepatitis B vaccine at birth. This combined tetravalent DTPwHB vaccine may play an important role to promote integration of HB vaccine into the Expanded Program of Immunization in hepatitis B-endemic areas.     

Immunogenicity of an inactivated hepatitis A vaccine in healthy children: two years' follow-up

To investigate the long-term immunogenicity of an inactivated hepatitis A vaccine in children, 100 healthy children, aged between 1 and 7 years old and all lacking the antibody to hepatitis A (HA) virus, were enrolled in this trial. They received 3 doses of strain HM 175 HA vaccine with 360 enzyme-linked immunosorbent assay (ELISA) units at 0, 1 and 6 months, respectively. Blood sampling for antibody and aminotransferases was performed 7 days before, then 1, 6, 7, 12, and 24 months after the first dose. The titers of antibody to HA virus were tested by radioimmunoassay and ELISA methods. All subjects became ELISA seropositive at Month 6 after two doses of vaccine. Except for one boy, 99 remained seropositive at Month 24, with a geometric mean titer of 1,148 mIU/ml. Antibody titers for females were significantly higher than those for males throughout the follow-up period. It was concluded that the inactivated HA vaccine used in the present trial was immunogenic and safe in children below seven years old. The vaccine-induced antibody persisted for at least two years in 99% of the vaccinees.     

The latest seroepidemiological pattern of hepatitis A in Japan

Age-specific prevalence of anti-hepatitis A virus antibody (anti-HAV) was surveyed with 2,708 sera collected in 1994 in various areas of Japan. By age-group analyses, we found strong association of anti-HAV antibody with higher age group. The prevalence ratios of antibody in the groups of 30-34, 35-39, 40-44, 45-49, 50-54, 55-59, 60-64 and 65 years or older were 0, 4.2, 22.0, 44.8, 57.6, 76.4, 84.5 and 91.4%, respectively. Geometric mean titers of anti-HAV antibody in the positive age groups were approximately 6,000 mIU/ml. The seropositives among older population were ascribed to the infections more than 40 years ago and the high anti-HAV titers have been maintained since that time. In Japan, people younger than 40 years of age are extremely risky to HAV infection, since 99% have no antibody. Those in forties are also risky since two-thirds of them are seronegative. In Japan, an inactivated vaccine was licensed in 1994. Vaccination may be recommended for such high-risk groups as travelers going to endemic areas, patients who have received blood product medication and child-care staffs.     

Safety and immunogenicity of a novel mammalian cell-derived recombinant hepatitis B vaccine containing Pre-S1 and Pre-S2 antigens in neonates

BACKGROUND: Most of the licensed hepatitis B vaccines produced by recombinant DNA contain the S protein component of the hepatitis B virus surface antigen particle but lack two important components, Pre-S1 and Pre-S2. These components have recently been shown to play an important immunogenic role by enhancing the hepatitis B surface antibody (anti-HBs) titers, stimulating response and circumventing genetic nonresponsiveness. OBJECTIVE: To assess safety, tolerability and immunogenicity in neonates of a novel recombinant HBV vaccine (Bio-Hep-B) containing the S, Pre-S1 and Pre-S2 components compared with a licensed recombinant vaccine (Engerix-B) containing the S component only. METHODS: Healthy neonates were randomized to receive either Bio-Hep-B (2.5 micrograms/dose) or Engerix-B (10 micrograms/dose) at ages < 24 h, 1 month and 6 months. Blood was obtained at ages 0, 1, 7 and 12 months. Tolerability was assessed by diary cards filled by the parents for 5 successive days after immunization. Immunogenicity was assessed by determination of anti-HBs antibody. RESULTS: Of 205 neonates 153 were in the Bio-Hep-B group and 52 were in the Engerix-B group. Both vaccines were well-tolerated and all infants became seroprotected (anti-HBs > 10 mIU/ml). After the first dose a significantly higher proportion of neonates seroconverted in the Bio-Hep-B group than in the Engerix-B group (83% vs. 34%; P < 0.001); this difference in seroresponse was even more pronounced for those achieving seroprotective concentrations (> 10.0 mIU/ml) after the first dose: 54% vs. 7%, respectively (P < 0.001). Geometric mean concentrations were significantly higher at all points in the Bio-Hep-B group. CONCLUSION: Both vaccines were well-tolerated and immunogenic. Bio-Hep-B, despite its low dose, was significantly more immunogenic and elicited more rapid antibody response. This finding has implication for future vaccine programs in regions where maternal screening for hepatitis B virus surface antigen and administration of hepatitis B immunoglobulin are not routinely practiced at birth for infants of hepatitis B virus carrier mothers.     

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.     

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.     

Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial

CONTEXT: Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem. OBJECTIVE: To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine. DESIGN: A multicenter, randomized, observer-blinded controlled trial. SETTING: Urban and suburban family medicine or pediatric practices. PARTICIPANTS: Two hundred eleven healthy toddlers aged 15 to 23 months. INTERVENTION: Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later. MAIN OUTCOME MEASURES: IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody. RESULTS: In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses. CONCLUSIONS: Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.     

A trichilemmal carcinoma arising from a proliferating trichilemmal cyst: the loss of the wild-type p53 is a critical event in malignant transformation

Active immunization against hepatitis B virus infection was carried out in 162 patients with acute lymphoblastic leukemia attending the Outpatient Department at Tata Memorial Hospital. Recombinant DNA vaccine was given in three doses at 0, 1 and 2 months followed by a booster 1 year after the first dose. Antibodies to hepatitis B surface antigen could be detected in 19.7% of patients following vaccination. Of these only 10.5% had titers in the protective range. Immunosuppression induced by both disease and treatment appears to diminish responsiveness to vaccination. Passive active prophylaxis with both vaccine and immunoglobulin may be a more effective alternative in these patients.     

Mania in young children

OBJECTIVE: To establish safety and immunogenicity of a reformulated whole cell pertussis based diphtheria-tetanus-pertussis vaccine (DTPw) at the 18-month booster stage following a 2, 4, and 6-month primary immunization course. METHOD: Open trial in suburban Melbourne in 100 healthy children initially recruited through maternal and child health centres. Thirty-five subjects were bled prior to vaccination, and 4-6 weeks after vaccination. A 7-day diary card was used to record subject temperatures and other systemic and local clinical signs. RESULTS: The increase in antibody geometric mean titres (GMT) after boosting was 19.5-fold (95%ci 14.2, 27.2) for tetanus and 26.5-fold (95%ci 16.6, 42.4) for diphtheria. Pertussis antibody GMTs also all showed substantial increases following the booster, with mean fold changes in titre ranging from 7.3 (Agg2) to 31.3 (Fha). Seventeen percent of subjects (95%ci 10%, 26%) experienced axillary temperatures > or = 38 degrees C during the 24-h period following vaccination. Low rates of significant (> 25 mm) injection site redness (13%) and swelling (8%) were recorded at 24 h postvaccination. CONCLUSION: This vaccine was well tolerated by children at 18 months of age, and showed substantial boosting of antibody to all components.