Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: implications for the timing of a booster dose

In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 µg or 40 g of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (<1 U/ml) antibodies before vaccination and to >400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (<0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (<0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid. Conclusion:10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered.     

Antibody persistence in five-year-old children who received a pentavalent combination vaccine in infancy

BACKGROUND: Antibody persistence was studied in 5.5-year-old Swedish children who in infancy completed a vaccine trial of a combined diphtheria toxoid, tetanus toxoid, acellular pertussis, inactivated polio and Haemophilus influenzae type b conjugate vaccine. Three priming doses at ages 2-4-6 months induced higher geometric mean concentrations of antibodies for all antigens than did two doses at 3-5 months, but there were no differences in proportions with protective antibody concentrations. After the booster dose administered at 13 or 12 months of age, respectively, there were no differences in concentrations or proportions between the groups. METHODS: In the present follow-up serum samples from 180 of the 228 vaccinees, 88 from the 4-dose and 92 from the 3-dose group, were 4.5 years later again tested for antibodies. RESULTS: The two groups did not differ significantly in antibody concentrations or proportions with antibodies above protective or other defined levels, with the exception of poliovirus type 3 (P < or = 0.01). In all 89% had > or = 0.01 IU/ml antibodies against diphtheria by enzyme-linked immunosorbent assay and 76% by the Vero cell neutralization test, 93% had > or = 0.01 IU/ml antibodies against tetanus, 96 to 99% had detectable antibodies against the polioviruses and 97% had > or = 0.15 microg/ml H. influenzae type b antibodies. As for pertussis only 44% had detectable antibodies against pertussis toxoid by enzyme-linked immunosorbent assay but 99% by Chinese hamster ovary cell neutralization test, and 94% had detectable antibodies against filamentous hemagglutinin. CONCLUSION: We found the persistence of antibodies satisfactory, with no clinically relevant differences in antibody concentrations demonstrated between children vaccinated according to a three dose or a four dose schedule in infancy.     

Seroprevalence of diphtheria and pertussis immunoglobulin G among children with pneumonia in Ji’nan,China

Background

Vaccination is still one of the most important methods to control and prevent childhood infections including diphtheria and pertussis. This study evaluated the level of diphtheria (DT) and pertussis (PT)-related antibodies among children with pneumonia in Ji’nan, China.

Methods

A total of 484 sera of children from 1?day to 13?years of age were collected from 2014 to 2015 in Ji’nan. Children with recent history of pertussis were excluded from this study. Anti-DT and PT IgG concentrations were measured by ELISA (Euroimmun, Lübeck, Germany).

Results

Of the 484 subjects tested, the overall positivity rate of anti-DT IgG (≥0.1?IU/ml) was 48.97%, and the highest positivity rate of anti-DT IgG (68.55%) and proportion with long term protection (23.27%) were observed in children aged 6?m-?<?3 y. For anti-PT IgG, 334 subjects (69.01%) had anti-PT IgG levels below the lower limit of detection (5?IU/ml). Even with detectable anti-PT antibodies, the majority (115/150, 76.67%) of them had antibody levels of 5-?<?40?IU/ml. The highest proportion of subjects with detectable anti-PT IgG (≥5?IU/ml) was observed in children aged <?6?m (44.36%), then the proportion continually decreased to 15.0% at 3 y-?<?6 y (χ²?=?24.05, p?<?0.0001). The highest positivity rate (≥40?IU/ml) was only 8.27% in children aged <?6?m. Subjects with an anti-PT IgG ≥100?IU/ml were observed in all the groups and there were no significant differences in the proportions of subjects with a level?≥?100?IU/ml among these age groups (χ²?=?2.572, p?=?0.4624). A total of 5 subjects had anti-PT IgG ≥100?IU/ml (≥1?years post pertussis vaccination) which was considered to be indicative of a recent pertussis infection.

Conclusions

We demonstrated low antibody levels and protection against pertussis in our study population. The anti-PT IgG maintained a low level throughout all age groups, and even no immune responses were observed after the basic immunization and booster. Our study supported the need to reevaluate the immune response of DTP vaccine which was used in Shandong province after 2010.

     

Antibodies against some bacterial antigens in children

The prevalence of bacterial antibodies was determined in 173 children aged 0–15 years. The prevalence of IgG Borrelia burgdorferi antibodies in titres > 500 in children less than 8 years of age was 6% while none of the older children had these antibodies in titres > 400. IgG Helicobacter pylori antibodies were detected only in children older than 6 years of age, with a prevalence of 6.5%, as were IgA H. pylori antibodies, with a prevalence of 3.7%. The prevalence of high-titre IgG Campylobacter jejuni antibodies was 1.2%, that of IgA 1.8% and IgM 1.2%. The prevalence of high-titre (> 500 IU/ml) antistreptolysin O was 3%, that of antistaphylolysin-alpha (≥ 4 IU/ml) 2% and that of antiteichoic acid antibodies (titre 2) 2%. Low-titre Yersinia antibodies were detected in 2%. High-titre Bordetella pertussis antibodies were detected in 6% of recently vaccinated children and in 8% of children in their first years of school. In the latter, high-titre antibodies were mainly of the IgM and IgA classes. Altogether 35 children tested positive for bacterial antibodies other than Bordetella pertussis antibodies. Clinical evaluation revealed a possible infection, suggested by the antibody, in 5 (3%) of the children. Two (vaccinated) children had evidence of whooping cough. Eight of the 35 children with high-titre bacterial antibodies (23%) also had elevated levels of autoantibodies (but not autoimmune diseases).     

Fifth vaccination with dipthteria, tetanus and acellular pertussis is beneficial in four- to six-year-olds

OBJECTIVE: Diphtheria, tetanus and pertussis serum antibody titers were assessed before a fifth dose of diphtheria-tetanus-acellular pertussis (DTaP) or diphtheria-tetanus-whole cell pertussis (DTwP) vaccination at age 4 to 6 years. METHODS: Healthy children who had participated in a series of National Institutes of Health-sponsored trials assessing DTwP and DTaP vaccines provided prevaccination sera before a fifth dose of DTwP or DTaP. The trial design was prospective, randomized and double blind. Diphtheria, tetanus and pertussis antibody titers were measured by enzyme-linked immunosorbent assay. Pertussis results are expressed in enzyme-linked immunosorbent assay units/ml based on US Food and Drug Administration reference sera. Tetanus and diphtheria toxin concentrations are expressed in IU/ml with a WHO international reference sera as a standard. RESULTS: For diphtheria 100% of the children had antibody titers above the minimum protective level of 0.01 IU/ml and 86 to 100% (depending on prior vaccine product) had titers >0.1 IU/ml. However, only 0 to 40% of the children had antibody titers > or =1.0 IU/ml, a titer associated with more certain durable protection. For tetanus none of the children had an antibody titer below 0.01 IU/ml, and 93 to 100% had titers > or =0.1 IU/ml, a titer associated with more certain, durable protection. For pertussis the geometric mean concentrations of antibody before booster were uniformly very low, and the percentage of children exceeding the minimum detectable titer of antibody by 4-fold was also low. CONCLUSION: Before a 4- to 6-year-old booster, a large proportion of children have titers of antibody to diphtheria below the certain, durable protective level. Because serologic correlates and minimum protective titers of antibody to pertussis antigens have not been established, the relevance of the low titers determined in the current study is unknown but a potential concern.     

Disorders of immune function in children with selective IgA deficiency

Numerous additional alterations of immune function in patients with selective IgA deficiency (serum IgA less than 0.05 g/l) have been described. In this group of patients we have investigated the connection with allergic diseases and alterations of the other immunoglobulin isotypes. Sera of 44 children from 1 3/12 to 18 years were analysed. In all patients serum IgA was below the nephelometric detection limit of 0.05 g/l). Using a more sensitive ELISA, IgA could be detected in all sera in concentrations ranging from 10 micrograms/l to 0.04 g/l. 25 children (57%) revealed a profound elevation of IgG serum levels, in 27 (61%) IgM was elevated above the upper age related normal value. In 7 patients (16%) with normal IgG serum levels a combined IgG2-IgG4 deficiency was found. In most cases these patients had unusually frequent and severe infections. Total IgE serum levels were determined by a RIA technique. In addition, an IgE-mediated sensitization to the most common food and inhalation antigens was detected by a standardized procedure (Phadiatop, Pharmacia). In 9/44 children (20%) IgE was less than 2 U/ml (lowest detection limit), 27 patients (62%) revealed levels of 6-86 U/ml within the age-related normal range. In 8 patients (18%) total IgE was above 381 U/ml. Four patients demonstrated a sensitization to inhalants, specific IgE antibodies to nutritive antigens were detected in three children.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long term follow up of serostatus after maternofetal parvovirus B19 infection

Background: Maternofetal parvovirus B19 infection may result in fetal hydrops or abortion. Chronic infection has been associated with long term complications (polyarthritis, persistent aplastic anaemia, hepatitis). In pregnancy maternal immunosuppression caused by a TH2 dominant response to viral antigens has been observed. There is little information on long term reactivity to intrauterine infection. Aims: To assess the serological status in children and their mothers after maternofetal parvovirus B19 infection and development of fetal hydrops. Methods: A total of 18 children and their mothers, and 54 age matched control infants were studied. Main outcome measures were parvovirus B19 DNA, specific IgM and IgG against the virus proteins VP1/VP2, and NS-1 in venous blood. Results: Parvovirus B19 DNA and antiparvovirus B19 (IgM) were undetectable in all sera. A significant larger proportion of maternal sera compared to study children''s sera contained IgG against the non-structural protein NS-1. Mean levels of VP1/VP2 IgG antibodies were significantly lower in the children than in their mothers (48 (36) v 197 (95) IU/ml). There was no history of chronic arthritis in mothers and children. Five women had subsequent acute but transient arthritis postpartum, which was not correlated with antibodies against NS-1. Conclusions: Serological evidence of persistent infection after maternofetal parvovirus B19 disease could not be detected. Increased maternal prevalence of anti NS-1 (IgG) and increased levels of antiparvovirus B19 (IgG) may reflect prolonged viraemia compared to fetal disease.     

Serological response to early measles vaccination

This study compares the persistence of measles IgG antibody in 239 children vaccinated at 6-8 months of age with 76 children vaccinated after 8 months of age. Among the children vaccinated prior to 9 months, 49 per cent of the children between 16 and 44 months and 33 per cent of children over 54 months had levels of measles IgG antibody conventionally considered protective. Among the children older than 48 months, 67 per cent of children vaccinated before 9 months and 13 per cent of children vaccinated after 8 months had antibody levels below the conventionally accepted protective levels of 0.2 IU/ml. Older children had lower antibody levels than younger children. Measles immunization before 9 months with the standard titer Edmonston-Zagreb vaccine has not provided a large proportion of under-five children with protective levels of measles IgG antibody. A significant proportion of children vaccinated at the currently recommended age also had suboptimal levels. It is difficult to protect the majority of the measles-susceptible population with a single dose regardless of the immunization schedule used. A second dose of measles vaccine may be necessary to increase the herd immunity.     

Antibodies to Plasmodium falciparum antigens vary by age and antigen in children in a malaria-holoendemic area of Kenya

BACKGROUND: Antibodies are important in protection against infection and disease caused by Plasmodium falciparum, but the frequencies of antibodies to multiple P. falciparum antigens in children are not well-characterized. METHODS: IgG and IgM antibodies to the vaccine candidate antigens circumsporozoite protein, thrombospondin-related adhesive protein, liver stage antigen-1, apical membrane antigen-1, erythrocyte-binding antigen-175 and merozoite surface protein-1 were measured by enzyme-linked immunosorbent assay in 110 children 0-50 months of age in a malaria holoendemic area of Kenya. RESULTS: A similar pattern was seen for IgG antibodies to circumsporozoite protein, thrombospondin-related adhesive protein, apical membrane antigen-1 and erythrocyte-binding antigen-175: high frequencies (70-90%) in children 0-4 months of age; a decrease in children 5-20 months of age (35-71%); and progressive increases in children 21-36 and 37-50 months of age (53-80% and 60-100%, respectively). In contrast, IgG antibodies to liver stage antigen-1 were infrequent in children 0-4 months of age (5%) and increased with age to 64%, and IgG antibody frequencies to merozoite surface protein-1 were similar across age groups (26-52%). IgG antibodies to all antigens were predominantly of the IgG1 and IgG3 subclasses. Frequencies of IgM antibodies to all antigens were low in children 0-4 months of age (0-15%) and increased with age (24-56% in the oldest children). CONCLUSION: In children in a malaria-holoendemic area, IgM antibody to all P. falciparum antigens is infrequent in the first 4 months of life but increases with age and increased exposure. The pattern of age-related IgG response frequencies to P. falciparum antigens varies significantly by antigen.     

Antibodies to pertussis antigens in pediatric health care workers

BACKGROUND: To compare the antibody concentrations against Bordetella antigens in health care workers in a pediatric hospital with those of two different populations without professional contact with children. METHODS: In a pediatric hospital 155 health care workers (135 female, 20 male), 292 male navy recruits after 3 months at sea and 146 regular blood donors (41 female, 105 male) were screened for antibodies of isotypes IgG and IgA to pertussis toxin (PT) and filamentous hemagglutinin (FHA) by enzyme-linked immunosorbent assay. RESULTS: Pediatric health care workers were positive for IgG anti-PT in 88%, for IgA anti-PT in 52%, for IgG anti-FHA in 99% and for IgA anti-FRA in 84%. Relative numbers for blood donors and recruits were 86 and 80% for IgG anti-PT, 56 and 55% for IgA anti-PT, 100 and 98% for IgG anti-FHA and 92 and 82% for IgA anti-FHA, respectively. Reverse cumulative distribution of all antibodies except for IgA anti-FHA showed no differences among the three groups; 2% of pediatric personnel, 3% of blood donors and 3% of navy recruits, respectively, had IgG anti-PT > or = 100 enzyme-linked immunosorbent assay units/ml, indicating a recent contact to Bordetella pertussis. CONCLUSION: Antibodies to B. pertussis antigens, such as IgG/IgA anti-PT and IgG/IgA anti-FHA, were similarly distributed in all three groups. Our results suggest that exposures leading to measurable immune responses to pertussis antigens in German pediatric health care workers are not significantly more frequent than in other populations without professional contacts with children.     

Long term follow up of serostatus after maternofetal parvovirus B19 infection.

BACKGROUND: Maternofetal parvovirus B19 infection may result in fetal hydrops or abortion. Chronic infection has been associated with long term complications (polyarthritis, persistent aplastic anaemia, hepatitis). In pregnancy maternal immunosuppression caused by a TH2 dominant response to viral antigens has been observed. There is little information on long term reactivity to intrauterine infection. AIMS: To assess the serological status in children and their mothers after maternofetal parvovirus B19 infection and development of fetal hydrops. METHODS: A total of 18 children and their mothers, and 54 age matched control infants were studied. Main outcome measures were parvovirus B19 DNA, specific IgM and IgG against the virus proteins VP1/VP2, and NS-1 in venous blood. RESULTS: Parvovirus B19 DNA and antiparvovirus B19 (IgM) were undetectable in all sera. A significant larger proportion of maternal sera compared to study children's sera contained IgG against the non-structural protein NS-1. Mean levels of VP1/VP2 IgG antibodies were significantly lower in the children than in their mothers (48 (36) v 197 (95) IU/ml). There was no history of chronic arthritis in mothers and children. Five women had subsequent acute but transient arthritis postpartum, which was not correlated with antibodies against NS-1. CONCLUSIONS: Serological evidence of persistent infection after maternofetal parvovirus B19 disease could not be detected. Increased maternal prevalence of anti NS-1 (IgG) and increased levels of antiparvovirus B19 (IgG) may reflect prolonged viraemia compared to fetal disease.     

Anti-diphtheric toxin antibodies in healthy children in kindergartens using the immunoenzymatic assay method

Although the immunization program for children in Indonesia follows the WHO recommendation, in some areas high diphtheric morbidity rates still occur for children under 5 years of age. This study deals with the ELISA for immunoglobulin G antibodies against diphtheric toxin in healthy children in kindergartens to determine the immunity status. One hundred and ninety eight samples of serum were collected from children of 18 kindergartens in West, East and South Denpasar districts and were investigated for IgG diphtheria using the ELISA method. History of immunization was obtained from the patient's immunization cards and an interview by the doctors. It was assumed to be immune when the IgG level was above 0.01 IU/ml. Eighty one out of 95 (85%) children from the control group (who had never had basic immunization) had IgG levels above 0.01 IU/ml and 81 out of 83 (97.6%) children from the group who had completed basic immunization (3 injections) had IgG level above 0.01 IU/ml. It seemed that natural infection played still a major role to develop immunity in those children.     

Effect of probiotics on vaccine antibody responses in infancy – a randomized placebo-controlled double-blind trial

Probiotics are immunomodulatory and may thus affect vaccine antibody responses. With the accumulating evidence of their health-promoting effects, probiotics are increasingly administered in allergy-prone infants. Therefore, we studied the effect of probiotics on antibody responses to diphtheria, tetanus and Haemophilus influenzae type b (Hib) vaccines in 6-month-old infants participating in a randomized placebo-controlled double-blind allergy-prevention trial. Mothers of unborn children at increased risk for atopy used a combination of four probiotic strains, or a placebo, for 4 wk before delivery. During 6 months from birth, their infants received the same probiotics and galacto-oligosaccharides, or a placebo. The infants were immunized with a DTwP (diphtheria, tetanus and whole cell pertussis) at ages 3, 4, and 5 months, and with a Hib polysaccharide conjugate at 4 months. Serum diphtheria, tetanus, and Hib IgG antibodies were measured at 6 months. In the probiotic group, protective Hib antibody concentrations (>/=1 microg/ml) occurred more frequently, 16 of 32 (50%) vs. six of 29 (21%) (p = 0.020), and the geometric mean (inter-quartile range) Hib IgG concentration tended to be higher 0.75 (0.15-2.71) microg/ml than in the placebo group 0.40 (0.15-0.92) microg/ml (p = 0.064). In these respective groups, diphtheria, 0.38 (0.14-0.78) vs. 0.47 (0.19-1.40) IU/ml (p = 0.449), and tetanus, 1.01(0.47-1.49) vs. 0.81 (0.56-1.39) IU/ml (p = 0.310), IgG titers were comparable. In conclusion, in allergy-prone infants probiotics seem not to impair antibody responses to diphtheria, tetanus, or Hib, but may improve response to Hib immunization.     

Decreased immune response to hepatitis B eight years after routine vaccination in Israel

BACKGROUND AND AIM: Although immunization of infants against hepatitis B virus (HBV) is the most effective way to prevent infection, duration of the afforded protection is unknown. Titers of anti-HBV antibodies decline with time, especially during the first few years after vaccination. Anti-HBV antibody levels were measured in the serum of vaccinated children in order to determine the duration of the response afforded by the primary course of HBV vaccine. METHODS: The immunity derived from the HBV vaccine was assessed by measuring antibody levels in 122 healthy children who were vaccinated in a routine vaccination program in Israel. RESULTS: Ninety-four children (77.1%) had detectable antibodies levels (HBsAb titer > or = 10 mIU/ml): 59 (48.4%) of the children had high antibodies levels (HBsAb titer > 100 mIU/ml). Twenty-eight children (22.9%) had undetectable antibodies levels (HBsAb titer < 10 mIU/ml). When the children were divided into three groups according to the time elapsed since vaccination, it was found that the antibody levels declined with time (p < 0.009). Most of the children with undetectable antibody levels belonged to the 5 to 8-y post-vaccination group (36.1% vs 20% and 14.6% for the 2.5 to 5-y and 1 to 2.5-y groups, respectively, p < 0.01). The mean HBsAb declined in relation to the length of time post-vaccination (226.9 +/- 248.2 mIU/ml for 1-2.5 y post-vaccination, 199.0 +/- 235.7 mIU/ml for 2.5-5 y and 90.4 +/- 138.5 for 5-8 y, p < 0.05). No correlation was found between HBsAb titers and gestational age, birthweight and parental origin, although females generated higher mean antibody levels than males (207.3 +/- 217 mIU/ml vs 141.9 +/- 218.9 mIU/ml, p < 0.05). CONCLUSION: Our data demonstrate a steady decline in anti-HBV titers over time after routine vaccination against HBV in Israel. The most significant decline occurred 5-8 y post-vaccination.     

History of whooping cough in nonvaccinated Swedish children, related to serum antibodies to pertussis toxin and filamentous hemagglutinin

The aim of this study was to examine whether there is a correlation between parental information on the child's history of whooping cough and the presence or absence of serum antibodies against two antigens of Bordetella pertussis, pertussis toxin and filamentous hemagglutinin, in nonvaccinated Swedish children. The parents of 266 Swedish children aged 1 to 4 years answered a questionnaire regarding the child's history of whooping cough, and a serum sample was obtained from the child for determination of IgG, IgM, and IgA antibodies to pertussis toxin and filamentous hemagglutinin. The study was performed from 1984 to 1986, five to seven years after the cessation of general vaccination against pertussis in Sweden; none of the children had received pertussis vaccine. Antibodies to both toxin and filamentous hemagglutinin increased with age. Of the children aged 4 years, 50% had antibodies to both antigens. Of all 266 children, 100 had antibodies to both antigens, 6 to toxin alone, and 49 to filamentous hemagglutinin alone. There was a good correlation between the presence of antibodies and a history of whooping cough. Of 91 children with a history of whooping cough, 77 had antibodies against both antigens and 13 against one antigen; only one child lacked detectable antibodies against both antigens. Of the 175 children with no history of whooping cough, 110 lacked detectable antibodies to both antigens, 23 had antibodies to both, 2 to toxin alone, and 40 to filamentous hemagglutinin alone. The data indicate that parental information on a previous history of whooping cough in their nonimmunized child is reliable, and that many infections with B. pertussis are subclinical or atypical. Exposure to other Bordetella species than B. pertussis, which is the only toxin-producing species, might be important for the development of FHA antibodies. A follow-up 2 to 4 years after the collection of serum samples of children without a history of whooping cough but with antibodies to one or both antigens indicated that serum antibodies to toxin, but not to filamentous hemagglutinin, may be protective against disease.     

Immunogenicity after one,two or three doses and impact on the antibody response to coadministered antigens of a nonavalent pneumococcal conjugate vaccine in infants of Soweto,South Africa

BACKGROUND: Children <6 months of age are at increased risk of pneumococcal disease. The early immunogenicity of conjugate vaccines therefore may be important to prevent disease in young children. OBJECTIVES: To determine the immunogenicity of a nonavalent pneumococcal conjugate vaccine after one dose, two doses and three doses and its impact on the antibody response to coadministered antigens. METHODS: A total of 500 infants from Soweto were immunized at 6, 10 and 14 weeks of age with either placebo (n = 250) or 9-valent pneumococcal conjugate vaccine (n = 250) containing serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F conjugated to CRM(197) mutant diphtheria protein. Blood was taken for determination of serotype-specific IgG before the first dose and 1 month after each dose. RESULTS: Before the first dose at 6 weeks of age >80% of infants had >0.15 microg/ml antibody to six of the nine antigens, >70% to serotypes 18C and 23F and >50% to serotype 4. Geometric mean concentrations (GMCs) after one dose ranged from 0.27 microg/ml for serotype 23F to 2.98 microg/ml for serotype 1; >90% of infants had serotype-specific antibody >0.15 microg/ml except for serotypes 23F (70%) and 6B (80%). After two doses GMCs ranged from 1.14 microg/ml for serotype 23F to 5.68 microg/ml for serotype 1; >95% of infants had serotype-specific antibody >0.15 microg/ml and >75% had >0.5 microg/ml for all nine serotypes. GMCs after three doses ranged from 2.73 microg/ml for serotype 23F to 6.18 microg/ml for serotype 5; >98% of infants had serotype-specific antibody >0.15 microg/ml and >92% had >0.5 microg/ml for all nine serotypes. Antibody concentrations after three doses were significantly higher to Haemophilus influenzae type b-polyribosylribitol phosphate vaccine in children who received pneumococcal conjugate vaccine, but they had lower antibodies to pertussis toxin than controls. CONCLUSIONS: A single dose of this pneumococcal conjugate vaccine produces a potentially protective antibody response to most serotypes in the majority of children in this population.     

Antibody response to Escherichia coli L-asparaginase. Prognostic significance and clinical utility of antibody measurement

By using a modification of the microtiter solid-phase radioimmunoassay, we have measured Escherichia coli L-asparaginase (L-ASP) specific IgG, IgG4, and IgE antibodies in children who received L-ASP as part of their chemotherapy for leukemia and lymphoma. In 13 children with acute lymphoblastic leukemia induced with vincristine, prednisone, and L-ASP (10,000 IU/M2 i.v. each week for 3 weeks), seven developed high titer specific IgG antibodies. Four of the seven relapsed at the time of their peaking IgG response (6-10 months). None of the six with low or absent L-ASP antibody response have relapsed (followed for 20-35 months). In six children with allergic reactions to L-ASP reinduction, all had high titers of L-ASP specific IgG4 (greater than or equal to 20 U/ml) at the time of their reaction. In 16 other children with low L-ASP IgG4 (less than 13 U/ml), none demonstrated allergic reactions to rechallenge. Specific IgE was not consistently detectable in either group. In 21 patients with leukemia or lymphoma on L-ASP with cyclophosphamide-containing regimens, none developed significant IgG antibody response, compared with seven of 13 not receiving cyclophosphamide (p less than 0.001). We conclude: (a) development of L-ASP antibodies may have prognostic significance; (b) the detection of specific IgG4 can predict L-ASP allergy; and (c) cyclophosphamide-containing regimens reduce antibody formation to L-ASP and may allow repetitive (without anaphylaxis) and more effective (avoiding neutralizing antibodies) use of L-ASP.     

百日咳疫苗接种对婴幼儿百日咳临床表现的影响

目的 探讨百日咳疫苗接种对婴幼儿百日咳临床表现的影响.方法 回顾性分析不同百日咳疫苗接种状态的百日咳婴幼儿临床表现及外周血细胞水平的差异.结果 共入组1083例<3岁百日咳患儿,其中未接种组551例,接种组532例;发病年龄<3月龄392例,含未接种372例,接种20例;≥3月龄691例,含未接种179例,接种512例...     

Efficacy and immunogenicity of acellular pertussis vaccine by manufacturer and patient age

Acellular pertussis vaccines, which have been used in Japan since 1981, vary in antigenic constituents among manufacturers. First, to assess the immunogenicity by manufacturer and patient age, 161 children aged 3 months to 2 years were immunized by acellular pertussis vaccine from one of three Japanese manufacturers, Biken, Takeda, or Kitasato. Anti-pertussis toxin antibody responses for children immunized with Takeda and Kitasato vaccines were comparable with patients with pertussis in the convalescent stage, and anti-pertussis toxin antibody response for Biken vaccine was far higher than those of convalescing patients. Anti-filamentous hemagglutinin antibody responses for the children given the three vaccines were far higher than those of the patients. Weak serotype 1.3 agglutinin responses were observed only in children administered the Takeda vaccine. Comparing these antibody responses among various age groups, the immunogenicity of acellular vaccines in children aged 3 to 6 months was comparable with children aged 2 years. Second, to assess the manufacturer-specific efficacy, 495 households of patients with pertussis were surveyed from 1981 to 1988. The estimated efficacy of the acellular pertussis vaccines in children aged 2 to 8 years was 82%, and there were no major differences in the secondary attack rates among children immunized with acellular pertussis vaccine from each manufacturer, ie, 12.5% (1/8) for Biken, 11.1% (2/18) for Takeda, and 5.9% (1/17) for Kitasato. We conclude from these two studies that similar efficacy was observed in children aged 2 years or older for acellular pertussis vaccines from the three manufacturers, which produced anti-pertussis toxin antibody responses comparable with patients with pertussis and far higher antifilamentous hemagglutinin antibody responses than in the convalescing patients, and that age did not affect the immunogenicity of acellular vaccines.     

Antibody response to Bordetella pertussis antigens after immunization with American and Canadian whole-cell vaccines.

Because of apparent differences in the incidence and epidemiology of pertussis in the United States and Canada, we measured the antibody response to four Bordetella pertussis antigens and to a whole-bacteria preparation in children immunized with American and Canadian whole-cell pertussis vaccines. All infants received combined pertussis, tetanus, and diphtheria vaccines from one of two American manufacturers or a single Canadian manufacturer. The Canadian children received either oral poliomyelitis vaccine, inactivated poliomyelitis vaccine as a separate injection, or a product that combined inactivated poliomyelitis vaccine with diphtheria, tetanus, and pertussis components. The Canadian trivalent diphtheria, tetanus, and pertussis vaccine given with oral poliovirus vaccine induced lower anti-pertussis toxin antibody titers than did the American vaccines (p < or = to 0.05) but higher antifimbriae and anti-69-kilodalton outer-membrane protein (pertactin) antibody titers (p < or = to 0.02). Canadian children immunized with inactivated poliomyelitis vaccine either as a separate injection or as a combined diphtheria, tetanus, and pertussis vaccine had consistently lower pertussis antibody titers than did those who received oral poliomyelitis vaccine (p < or = 0.001). We conclude that there is a wide range of antibody responses to B. pertussis antigens after immunization with various whole-cell pertussis vaccines, and that these responses may be influenced by concurrent administration of other vaccines.