Response of preterm infants to diphtheria-tetanus-pertussis immunizations

To establish guidelines for the routine use of diphtheria, tetanus, and pertussis (DTP) vaccine in preterm infants, we quantitated antibody responses of preterm infants to DTP and determined the nature and extent of side effects. Twenty-five preterm infants were immunized with 0.5 ml DTP vaccine at routine intervals. Term infants served as controls. Immediately before each immunization and 2 months after the third, DTP-specific antibodies were quantitated. Clinical side effects were determined by parental report. After the second immunization, 100% of preterm infants had evidence of specific antibody production against diphtheria, tetanus, and pertussis. The incidence of side effects was low, but irritability was significantly more common in preterm infants after the second immunization. These observations suggest that the initiation of primary immunization with DTP in preterm infants need not be delayed beyond 2 months of age.     

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.     

Comparison of acellular and whole-cell pertussis-component DTP vaccines. A multicenter double-blind study in 4- to 6-year-old children

An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.     

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Combined diphtheria, tetanus, pertussis, and Haemophilus influenzae type b vaccines for primary immunisation

A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to assess antibody response. Data were compared with those from historical controls who had received DTP and PRP-T vaccines by separate injection. The combined vaccine was well tolerated. Rates of local and general reactions were similar to those reported for infants immunised by separate injection. All infants achieved protective antibody titres (> 0.01 IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15 microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3) showed appreciable rise following immunisation. DTP and PRP-T vaccines provide similar antibody responses and adverse effects whether mixed in the same syringe or administered by separate injection. The vaccines could be combined for use in the United Kingdom primary immunisation schedule.     

Pyrexia after diphtheria/tetanus/pertussis and diphtheria/tetanus vaccines.

The temperatures of 587 children were taken before and after diphtheria/tetanus/pertussis (DTP) or diphtheria/tetanus (DT) vaccine. Only slight temperature increases were found but these were notably more frequent after plain than adsorbed DTP vaccine preparations and the frequency increased with each successive dose.     

Combined diphtheria,tetanus, pertussis,and Haemophilus influenzae type b vaccines for primary immunisation.

A total of 146 infants were immunised at ages 2, 3, and 4 months with a combined diphtheria, tetanus, pertussis (DTP)--Haemophilus influenzae type b (Hib) tetanus toxoid conjugate (PRP-T) vaccine (Pasteur Merieux) to assess the antibody response and adverse events associated with immunisation. Adverse events, including fever, were recorded by parents in a diary for three days following each injection. Blood was taken before the first immunisation and four weeks after the third immunisation to assess antibody response. Data were compared with those from historical controls who had received DTP and PRP-T vaccines by separate injection. The combined vaccine was well tolerated. Rates of local and general reactions were similar to those reported for infants immunised by separate injection. All infants achieved protective antibody titres (> 0.01 IU/ml) for diphtheria and tetanus; 98% acquired Hib (PRP) antibody > 0.15 microgram/ml and 82.5% > 1.0 microgram/ml. Pertussis antibody titres (pertussis toxin, filamentous haemagglutinin, total agglutinins, and agglutinins 2 and 3) showed appreciable rise following immunisation. DTP and PRP-T vaccines provide similar antibody responses and adverse effects whether mixed in the same syringe or administered by separate injection. The vaccines could be combined for use in the United Kingdom primary immunisation schedule.     

Vaccination rate and age of premature infants weighing <1500 g: a pilot study in north-western Switzerland

In Switzerland, there are no special vaccination recommendations for premature and low-birthweight infants with respect to a particular target vaccination age. Incomplete and delayed vaccination bears the inherent risk of preventable infections. Therefore, the vaccination rate and age of 60 premature infants in north-western Switzerland born in 1994/95 were investigated in a retrospective case-control study. For this group of patients these are the first data ever available for this region. At the age of 4-5 y, the vaccination rates for polio and diphtheria, tetanus, pertussis (DTP acellular) as well as Haemophilus influenzae b (Hib) were similar in both preterm and full-term infants. In both groups, the fourth dose of vaccine against DTP, Hib and polio was far less frequently administered than the first three. The vaccination age in preterm infants for most vaccinations was significantly higher than in age-matched full-term controls. This was particularly obvious for the first dose of vaccine against polio and DTP. In preterm infants, the median age (5th; 95th percentile) at the date of the first polio vaccination was 131 (89; 270) d and 82 (60; 182) in full-term controls (p < 0.00001). The age difference was even larger for the first DTP vaccination (62 d, p < 0.00001). The main reasons for delayed vaccination may include insufficient information given to parents as well as prolonged hospitalization. Conclusion: Vaccination of preterm infants should be discussed in every discharge communication, with emphasis on vaccine administration at the appropriate chronological age.     

Prevention of pertussis among adolescents: recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine

The purpose of this statement is to provide the rationale and recommendations for adolescent use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Despite universal immunization of children with multiple doses of pediatric diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine, pertussis remains endemic with a steady increase in the number of reported cases. Two peaks in the incidence of pertussis occur in pediatric patients: infants younger than 6 months of age who are inadequately protected by the current immunization schedule and adolescents 11 through 18 years of age whose vaccine-induced immunity has waned. Significant medical and public health resources are being consumed in postexposure management of adolescent cases, contacts, and outbreaks with little beneficial effect on individuals or the epidemiology of disease. Two Tdap products were licensed in 2005 for use in people 10 through 18 years of age (Boostrix) and 11 through 64 years of age (Adacel). The American Academy of Pediatrics recommends the following: 1. Adolescents 11 to 18 years of age should receive a single dose of Tdap instead of tetanus and diphtheria toxoids (Td) vaccine for booster immunization. The preferred age for Tdap immunization is 11 to 12 years. 2. Adolescents 11 to 18 years of age who have received Td but not Tdap are encouraged to receive a single dose of Tdap. An interval of at least 5 years between Td and Tdap is suggested to reduce the risk of local and systemic reactions; however, intervals of less than 5 years can be used, particularly in settings of increased risk of acquiring pertussis, having complicated disease, or transmitting infection to vulnerable contacts. Data support acceptable safety with an interval as short as approximately 2 years. 3. Tdap and tetravalent meningococcal conjugate vaccine (MCV4 [Menactra]) should be administered during the same visit if both vaccines are indicated. If this is not feasible, MCV4 and Tdap can be administered using either sequence. When not administered simultaneously, the American Academy of Pediatrics suggests a minimum interval of 1 month between vaccines. The rationale for this strategy is to provide direct protection of immunized adolescents. With implementation of vaccine recommendations, indirect benefitalso is likely to extend to unimmunized peers and other age groups. The strategy of universal Tdap immunization at 11 to 12 years of age is cost-effective.     

Safety and immunogenicity of acellular pertussis vaccine combined with diphtheria and tetanus toxoids in 17- to 24-month-old children.

A double-blind, randomized, controlled trial comparing 4 lots of acellular pertussis-diphtheria tetanus toxoids vaccine (APDT) to whole cell DTP vaccine in 397 children was conducted at 7 clinical centers. Children were immunized at 17 to 24 months of age and sera were obtained pre- and postimmunization. Sera were analyzed for antibody to pertussis antigens (pertussis toxin, filamentous hemagglutinin, with a molecular weight of 69,000 (69k) outer membrane protein and agglutinogens) and to diphtheria and tetanus toxoids. Information concerning local reactions and systemic events was collected daily for 10 days postimmunization. The acellular vaccine produced significantly fewer local reactions than whole cell DTP. Parents reported that drowsiness or fretfulness occurred significantly less often in APDT vaccine recipients compared with whole cell DTP recipients. Fever greater than or equal to 38.3 degrees C occurred in 8% of APDT vaccine recipients and in 15% of whole cell DTP vaccine recipients (P = 0.06). The only significant difference in immune response to pertussis antigens between the two vaccines was for filamentous hemagglutinin (P less than 0.01) for which significantly higher antibody concentrations were found in the APDT vaccine group. We conclude that this APDT vaccine is safe and immunogenic when administered as a booster dose to 18-month-old children.     

IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization

To evaluate immune responses to diphtheria and tetanus toxoids in infants we used enzyme-linked immunosorbent assays to detect total IgG and specific IgG-1, IgG-2, IgG-3, and IgG-4 antibody. One group of infants received a newborn dose and subsequently received the usual three doses of DTP. A second group of infants received only the routine dosage at 2, 4, and 6 months of age. In sera acquired at birth, 6, and 9 months of age, there were no statistically significant differences between the two vaccine groups in IgG antibody responses to diphtheria or tetanus, or in IgG subclass tetanus-specific antibody responses. In individual children, tetanus-specific subclass responses were similar in pattern to that for total IgG tetanus antibody, i.e. each IgG subclass response appeared to be regulated by similar mechanisms in that child, but the regulation differed between children. In contrast to a prior study of pertussis immunity, maternally acquired antibody did not significantly affect immune responses to diphtheria or tetanus toxoid by 9 months of age. There was no discernible tolerance due to early tetanus or diphtheria immunization or to high levels of maternally acquired antibody.     

Pertussis epidemic in Oklahoma. Difficulties in preventing transmission

From Jan 1 to Dec 31, 1983, 351 cases of pertussis were reported in Oklahoma. Overall, 59% of the cases were among children 3 months to 6 years of age, the target age group for pertussis vaccination; only 42% of the patients in this age group were appropriately immunized for age with diphtheria and tetanus toxoids and pertussis vaccine (DTP). A survey of 185 households in the neighborhoods of three cases found that only 65% of 57 children 3 months to 6 years of age were appropriately immunized for their age. Aggressive control of the outbreak was attempted in Oklahoma County with recommendations for widespread vaccination against pertussis. However, the effort failed to immunize 82% of the 931 children in the initial target group. Nonetheless, analysis of the reported cases suggested that less than one fourth of the cases were potentially preventable by a single additional dose of DTP, ie, in individuals 3 months to 6 years of age with a history of at least one prior dose of DTP who were not appropriately immunized for age. The optimal solution to outbreak control is outbreak prevention by ensuring that the maximal number of children younger than 7 years of age receive routine age-appropriate DTP vaccination.     

Response of preterm infants to diphtheria-tetanus-pertussis vaccine

The American Academy of Pediatrics recommendation that immunization of preterm infants with diphtheria-tetanus-pertussis (DTP) vaccine should begin at 2 months after birth, regardless of gestational age, is based on limited data. A prospective study was conducted to determine the immunogenicity and safety of DTP vaccine in preterm infants. One hundred ten preterm and 146 full term infants received doses of DTP at 2, 4 and 6 months after birth. Adjusted analysis of the antibody responses indicated that after three doses mean titers among preterm infants to each vaccine component were comparable to those of full term infants. Adjusted analysis of the incidence of adverse events indicated that the risk of adverse events in preterm infants was not significantly higher than that in full term infants. DTP vaccine is immunogenic and safe in preterm infants when the series is initiated at 2 months after birth, and this study supports the current recommendation of the American Academy of Pediatrics.     

Influence of parental knowledge and opinions on 12-month diphtheria, tetanus, and pertussis vaccination rates

To assess the magnitude and cause of decreasing diphtheria, tetanus toxoids, and pertussis (DTP) immunization rates, a retrospective cohort study investigated the immunization status against pertussis among 1-year-old children in Utah. Questionnaires were sent to the parents of 2975 children born in June 1985. Parents were asked about each child's DTP immunization status, including the number, type, and dates of the vaccinations, reasons for or against vaccination, and their knowledge of whooping cough and the vaccine. Children were considered adequately immunized against pertussis when they had received three DTP vaccinations by their first birthday. In Utah, the lack of pertussis immunization among young children is a serious problem: greater than 30% of 1-year-old children were not adequately protected. Accurate parental knowledge about the relative risks of vaccination and illness was associated with a greater likelihood for immunization. Although some parents chose to forego the vaccination because they were concerned about its side effects, the most common reason for incomplete immunization was illness at the time the vaccination was to be given. If immunization rates are to improve, health care professionals must not only make an effort to educate the general population regarding the vaccine, but they must also ensure immediate follow-up for immunization when the procedure is delayed.     

Acellular pertussis vaccine given by accelerated schedule: response of preterm infants

OBJECTIVE: To describe the immune response of preterm infants to a diphtheria/tetanus/three component acellular pertussis (DTaP) vaccine, under an accelerated schedule, and the effects of steroids on this response. To compare responses with those of term infants. DESIGN: Prospective observational study. SETTING: Five Wessex neonatal units; Hertfordshire immunisation clinics. PATIENTS: Infants born at < 32 weeks; term controls. INTERVENTIONS: DTaP-Haemophilus influenzae type b vaccine given at 2, 3, and 4 months. Blood taken to assess antibody responses to vaccines. MAIN OUTCOME MEASURES: IgG geometric mean concentrations (GMC) to vaccines. RESULTS: A total of 130 preterm (mean gestational age 29.1 weeks) and 54 term infants were recruited. After the third immunisation, preterm infants had similar GMCs to controls to diphtheria, tetanus, filamentous haemagglutinin (FHA), and pertactin (PRN), but a significantly lower GMC to pertussis toxin (PT). Responses to tetanus and PRN increased with age at the third immunisation, and those to tetanus, FHA, PRN, and PT increased with gestational age at birth. Response to tetanus correlated negatively with the number of doses of antenatal steroids received. There was no association between responses and postnatal steroids. CONCLUSION: When immunised with a combined acellular pertussis- H influenzae type b vaccine under an accelerated schedule, IgG GMC of preterm infants to PT was reduced. GMCs to tetanus, FHA, PRN, and PT increased with gestational age at birth, and GMCs to tetanus and PRN increased with age at the third immunisation. There is, however, no benefit in delaying immunisation. Anti-tetanus IgG decreased with increasing number of doses of antenatal steroids. There was no effect for postnatal steroids.     

Long-term clinical effectiveness of an acellular pertussis component vaccine and a whole cell pertussis component vaccine

The objective of this open study was to monitor the long-term effectiveness of the Lederle-Takeda diphtheria and tetanus toxoids and acellular pertussis antigen(s) (DTaP) vaccine and the Wyeth-Lederle diphtheria and tetanus toxoids and pertussis whole cell (DTP) vaccine in children who had received four doses of vaccine at 3, 4.5, 6 and 15 months of age during a pertussis vaccine efficacy trial from May 1991 to December 1994. After unblinding of the study code, follow-up information was obtained by use of standardised questionnaires twice a year from 1995 to 2000 to detect clinical pertussis and cough illnesses > or = 14 days duration. Physician confirmation was sought for all reported cases. Rates of reported cough illnesses > or = 14 days duration and rates of parent and physician diagnosed pertussis in former DTaP, DTP and diphtheria and tetanus toxoids (DT) recipients were determined and vaccine efficacy was calculated. Nine questionnaires were sent to parents of 2924 study children of whom 349, 1304 and 1271 had originally received DT, DTaP and DTP, respectively. Overall, rates for cough illnesses (per 100 person years) were similar among the vaccine groups suggesting that reporting bias was not a major factor. Calculated efficacy for the 6-year follow-up period based upon physician diagnosed pertussis was 89% (95% CI=79 94) for DTaP and was 92% (95% CI=84-96) for DTP. CONCLUSION: no evidence of decreasing efficacy over time was noted.     

DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation

Aims: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. Methods: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. Results: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 µg/ml with 80% ⩾0.15 µg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% ⩾8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with ⩾80% achieving protective rises in IgG against the five pertussis antigens. Conclusion: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.     

DT5aP-Hib-IPV and MCC vaccines: preterm infants' response to accelerated immunisation.

AIMS: To describe the immune response of preterm infants to combined diphtheria/tetanus/5 component acellular pertussis-Haemophilus influenzae type b inactivated polio vaccine (DT5aP-Hib-IPV) and meningococcal serogroup C conjugate vaccine (MCC) under accelerated schedule. To compare results with term infants immunised with DT5aP-Hib-IPV and with historical data from preterm infants immunised with a DT3 component aP-Hib vaccine. METHODS: Prospective observational study in preterm infants born at <32 weeks gestation with comparison to contemporary cohort of term infants. DT5aP-Hib-IPV and MCC vaccines were given at 2, 3, and 4 months. RESULTS: Fifty preterm infants (mean gestational age 28.5 weeks) completed the study. After three doses of vaccines Hib polysaccharide IgG geometric mean concentration (GMC) was 1.21 microg/ml with 80% > or =0.15 microg/ml; MCC serum bactericidal assay geometric mean titre (GMT) was 1245 with 100% > or =8. All infants achieved protective titres to diphtheria, tetanus, and the three poliovirus types with > or =80% achieving protective rises in IgG against the five pertussis antigens. CONCLUSION: Preterm infants immunised with DT5aP-Hib-IPV and MCC vaccines show IgG responses to Hib and MCC greater than seen historically in both term and preterm infants with a DT3aP-Hib vaccine, and for pertussis antigens and poliovirus type 1 responses similar to that seen in term infants immunised with DT5aP-Hib-IPV. Responses to poliovirus types 2 and 3 are reduced, but all infants achieved protective titres.     

Clinical and serologic responses to acellular pertussis vaccine in infants and young children

We administered diphtheria, tetanus, and pertussis (DTP) vaccine containing acellular (lymphocytosis promoting factor and filamentous hemagglutinin) pertussis vaccine to three groups of 20 children each (4 to 6 years, 17 to 21 months, and 5 to 9 months of age). All the children tolerated the vaccine well; no reactions occurred that contraindicated further immunization. Older children had significantly more local (redness or swelling) and systemic (fever or fretfulness) reactions than younger children. Eighty percent to 90% of the children in the two older age groups had fourfold or greater increases in antibody titers to DTP antigens one month after vaccination. The postvaccine concentrations of antibody to tetanus and diphtheria were greater than 0.01 IU/mL in all children. Serologic responses to lymphocytosis promoting factor and filamentous hemagglutinin varied with age; significantly more older children than younger children had four-fold or greater increases. Acellular pertussis DTP vaccine was antigenic in young children and was less reactogenic than standard whole cell DTP vaccine according to rates reported in previous studies.     

Haemophilus influenzae type b conjugate vaccine trial in Oxford: implications for the United Kingdom.

The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed and the incidence of minor side effects was no greater in the recipients of H influenzae type b conjugate vaccine. Two doses of the vaccine (standard and low) were compared: geometric mean titres of serum anticapsular antibody rose from 0.11 microgram/ml before immunisation to 26.4 micrograms/ml after three immunisations with the standard dose and 14.6 micrograms/ml with the low dose. The geometric mean titre among 21 unimmunized infants at this age was 0.06 micrograms/ml. Both doses therefore generated antibody concentrations likely to be protective after three immunisations. There were no non-responders. Incorporation of an H influenzae type b conjugate vaccine into the primary immunisation schedule has the potential for preventing over 1000 cases of systemic H influenzae type b disease and 50 deaths each year in the United Kingdom.