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.     

Mucosal immune responses to meningococcal conjugate polysaccharide vaccines in infants

BACKGROUND: Serogroup C meningococcal conjugate polysaccharide vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants. Because meningococcus is a mucosal pathogen colonizing the nasopharynx, local mucosal immune responses may play an important role in host defense against infection and carriage. We have investigated the mucosal IgA and IgG antibody responses to two meningococcal C conjugate vaccines in the saliva of healthy infants. METHODS: Specific salivary IgA and IgG antibodies to two meningococcal C polysaccharide conjugate vaccines (Menjugate from Chiron Corp., n = 46; and Meningitec from Wyeth Lederle, n = 54) were investigated by immunoassay in infants after parenteral vaccinations at the ages of 2, 3 and 4 months. Unstimulated saliva samples were collected immediately before the first immunization and 1 month after the third immunizations. Forty healthy infants receiving the same routine vaccines but no meningococcal C vaccine were recruited as controls. RESULTS: There were significant increases in meningococcal C polysaccharide-specific IgG antibody concentrations postvaccination compared with prevaccination concentrations in both vaccinated groups (both P < 0.001), but no change in the control group. There were no significant increases in specific IgA postvaccination geometric mean concentrations in either the vaccine or the control groups. The number of IgA positives postvaccination increased slightly in the Wyeth vaccine group vs. controls (P < 0.05). CONCLUSIONS: Significant salivary IgG antibodies to meningococcal C polysaccharide were observed after parenteral immunization with two meningococcal C conjugate vaccines, whereas there was no significant increase in specific IgA antibody levels for these two vaccines.     

Reconsideration of the use of meningococcal polysaccharide vaccine

In 2005, a quadrivalent meningococcal conjugate vaccine was licensed in the United States for persons aged 11-55 years of age. For children aged 2-10 years with underlying diseases associated with increased risk of meningococcal disease, unconjugated meningococcal polysaccharide (MPS) vaccination is still recommended. This article reviews the increasing evidence that MPS vaccination impairs serum anticapsular antibody responses to subsequent injections of MPS or meningococcal conjugate vaccines (antibody hyporesponsiveness). Administering MPS as a probe to assess conjugate vaccine-induced immunologic memory also can extinguish subsequent memory anticapsular antibody responses, whereas conjugate vaccination regenerates memory B cells. Whether induction of antibody hyporesponsiveness or loss of immunologic memory increase the risk of acquiring meningococcal disease remains speculative. However, for children at increased risk of meningococcal disease, immunization with meningococcal quadrivalent conjugate vaccine off-label instead of MPS vaccine should be considered. Requirements for licensure of new glycoconjugate vaccines that include performing comparative clinical trials to demonstrate noninferiority with MPS vaccine, or use of a MPS challenge to assess conjugate-induced immunologic memory also should be modified because there are safer approaches for obtaining the same information.     

Evaluation of a diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b vaccine given concurrently with meningococcal group C conjugate vaccine at 2, 3 and 4 months of age.

BACKGROUND AND OBJECTIVE: In view of the possible introduction of diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib, eg Pediacel) vaccine in the UK, a study of the immunogenicity of Pediacel when given with one of two different meningococcal group C conjugate (MCC) vaccines at 2, 3 and 4 months of age was conducted. METHODS: Randomised controlled study in 241 infants. RESULTS: Post vaccination, the proportion of infants with anti-polyribosylribitol phosphate (PRP) levels > or =0.15 microg/ml was 93.2% (95% confidence interval (CI) 86.6 to 96.7) in the Pediacel group compared with 100% (95% CI 96.4 to 100) in the diphtheria-tetanus-whole-cell pertussis-Haemophilus influenzae type b (DTwP-Hib) group. The anti-PRP response was lower in infants receiving either Pediacel or DTwP-Hib when these vaccines were given concomitantly with meningococcal group C conjugate with diphtheria-derived protein CRM(197) as conjugate protein (MCC-CRM) compared with meningococcal group C conjugate with tetanus toxoid as conjugate protein (MCC-TT). For group C meningococcus, the proportion of infants with serum bactericidal antibody (SBA) titre > or =1:8 in the Pediacel group was 99.0% compared with 100% in the DTwP-Hib group. The MCC SBA geometric mean titre (GMT) was lower in those receiving Pediacel with MCC-TT than in those receiving DTwP-Hib with MCC-TT, although all titres were well above the protective threshold. The MCC SBA GMT was similar in those receiving Pediacel and DTwP-Hib and MCC-CRM. Responses to all other vaccine components were equivalent in the two groups. CONCLUSIONS: Pediacel is immunogenic when given at 2, 3 and 4 months of age. Coadministration of MCC vaccine can influence the Hib response, and the MCC response to a tetanus conjugate can be influenced by the nature of the coadministered DTP-Hib vaccine.     

Safety and immunogenicity of meningococcus serogroup C conjugate vaccine administered as a primary or booster vaccination to healthy four-year-old children

BACKGROUND: Meningococcal C conjugate (Men C) vaccines have been routinely used in the UK since November, 1999. Little information exists regarding antibody persistence or immunologic memory after infant vaccination or response to a first dose at 4 years. METHODS: Ninety-five children immunized at 2, 3 and 4 months of age with 0 or 3 doses of Men C vaccine, boosted with Men C or meningococcal A/C polysaccharide vaccine at 12 months, received a single dose of Men C vaccine at 4 years; 103 age-matched controls were recruited. Pre- and postvaccination Men C IgG (enzyme-linked immunosorbent assay) antibody titers and serum bactericidal activity (SBA) were measured. Safety data were also collected. RESULTS: Baseline SBA titers of > or =1/4 were observed in 87% of children after at least 3 doses of Men C vaccine in infancy compared with 21% of controls. Reciprocals of postvaccination SBA geometric mean titers in those with four prior doses [3803 (95% confidence interval 3489, 4146)] were significantly higher than controls [33 (95% confidence interval 20, 55)] ( < 0.001). Memory was attenuated by the 12-month meningococcal A/C polysaccharide booster [734 (95% confidence interval 484, 1115)] ( < 0.001). All children had IgG responses to a first dose of Men C vaccine, 80% achieving SBA titers of > or =1/4 (77% > or =1/8). The vaccine was safe and well-tolerated. CONCLUSION: Infant immunization with Men C produced persistent antibody and immunologic memory at 4 years. All children made IgG antibodies after a first dose at this age, with 80% showing bactericidal activity. Clarification of the best measures of Men C vaccine-induced protection is needed, through correlation of immunogenicity data such as this with UK vaccine efficacy estimates.     

Lack of serum bactericidal activity in preschool children two years after a single dose of serogroup C meningococcal polysaccharide-protein conjugate vaccine

BACKGROUND: There is an increased risk of invasive meningococcal disease during the teenage years. A cohort of children vaccinated with a single dose of meningococcal C protein-polysaccharide conjugate (MenC) vaccine in early childhood during the U.K. catch up campaign will enter this age group during the coming decade. The duration of protective immunity against invasive meningococcal C disease provided by this single dose regimen is uncertain.A serum bactericidal titer of <1/8 correlates with susceptibility to invasive meningococcal disease. We assessed this correlate of protection in a cohort of children approximately 2 years after a single dose of vaccine. METHODS: Serum bactericidal activity was assessed in 94 children (median age, 4.0 years) at a median time of 1.8 years after vaccination. RESULTS: Of the 94 children, 59 (63%) had a serum bactericidal titer <1/8. CONCLUSION: The data from this study add to previous evidence indicating that immunity wanes rapidly after vaccination with serogroup C meningococcal glycoconjugate vaccines in infancy and early childhood. Such observations suggest that booster doses of MenC vaccine may be needed to maintain the successful contribution this vaccine has made to child health in the United Kingdom.     

Safety and immunogenicity of three doses of a Neisseria meningitidis A + C diphtheria conjugate vaccine in infants from Niger

BACKGROUND: High rates of endemic disease and recurrent epidemics of serogroup A and C meningococcal meningitis continue to occur in sub-Saharan Africa. A meningococcal A + C polysaccharide diphtheria-toxoid-conjugated vaccine may address this issue. METHODS: In Niger three doses of a bivalent meningococcal A + C diphtheria-toxoid-conjugated vaccine (MenD), containing 1, 4 or 16 microg of each polysaccharide per dose, administered at 6, 10 and 14 weeks of age, were compared with Haemophilus influenzae type b-tetanus toxoid-conjugated (PRP-T) vaccine given with the same schedule or with a meningococcal A + C polysaccharide vaccine (MenPS) given at 10 and 14 weeks of age. One blood sample was taken at the time of enrollment (6 weeks of age) and another was taken 4 weeks after the primary series. RESULTS: All doses of MenD were well-tolerated. After the primary series a higher proportion of infants had detectable serum bactericidal activity against serogroup A for each dose of MenD (from 94% to 100%) than for MenPS (31%) or H. influenzae type b-tetanus toxoid-conjugated vaccine (18.9%); P < or = 0.05. Significant differences were also observed for serogroup C MenD 4 microg or MenD 16 microg (100%) vs. MenPS (69.7%) or Haemophilus influenzae type b-tetanus toxoid-conjugated vaccine (24.3%); P < or = 0.05. When MenPS vaccine was given to 11-month-old children, the immune response measured by both enzyme-linked immunosorbent assay and serum bactericidal assay was greater in those previously immunized with MenD than in those immunized with MenPS vaccine. CONCLUSION: MenD was safe among infants in Niger, and immunization led to significantly greater functional antibody activity than with MenPS. The 4-microg dose of MenD for both the A and C serogroups has been selected for further studies.     

Safety and immunogenicity of four doses of Neisseria meningitidis group C vaccine conjugated to CRM197 in United States infants

BACKGROUND: Following widespread use of conjugate pneumococcal vaccine, Neisseria meningitidis likely will become the leading cause of bacterial sepsis and meningitis in US children. This report describes the safety and immunogenicity in US children of four consecutive doses of a meningococcal group C vaccine conjugated to CRM197 via reductive amination (MnCC). METHODS: One hundred six healthy 2-month-old infants received MnCC at 2, 4 and 6 months of age in a randomized, controlled double blind study; children in the other treatment arm were given a 7-valent conjugate pneumococcal vaccine. Parents reenrolled 64 of these children at 12 to 15 months to receive a fourth dose of MnCC. Routine childhood vaccines, including DTP, were coadministered. Temperatures and symptoms were recorded for 3 days after each immunization. Serum enzyme-linked immunosorbent assay IgG and bactericidal antibodies were measured prevaccination and before and 1 month after Doses 3 and 4. RESULTS: Moderate to severe local reactions, defined as erythema or induration > or =2.4 cm or pain that interfered with limb movement was reported after 0 to 3.2% of MnCC injections, depending on the reaction and dose. Fever occurred in 23 to 37% of children, but the contribution of MnCC to the febrile reactions is unknown. Geometric mean concentrations of IgG antibody to group C meningococcal polysaccharide were 3.72 microg/ml after Dose 3 and 8.03 microg/ml after the booster. Geometric mean functional serum bactericidal antibody titers after Doses 3 and 4 were 1:463 and 1:2341, respectively. One hundred percent of children had a serum bactericidal antibody titer of > or =1:64 after three doses and > or = 1:128 after the booster. CONCLUSIONS: The MnCC vaccine had an acceptable safety profile and generated high titers of bactericidal antibody in immunized US infants and toddlers. It appears to be an attractive candidate vaccine for the prevention of serogroup C meningococcal disease in young children.     

Immunogenicity of a serogroup B meningococcal vaccine against multiple Neisseria meningitidis strains in infants.

BACKGROUND: The serogroup B meningococcus is responsible for the majority of cases of meningococcal disease in temperate countries. Infants and young children <2 years of age are at greatest risk of disease. This study assessed the immunogenicity in infants of a serogroup B meningococcal outer membrane protein vaccine that has been used extensively in disease outbreaks in Cuba and several Latin American countries and shown to be efficacious in teenagers. METHOD: One hundred five healthy infants entering the routine vaccination schedule in Havana, Cuba, were given either 2 or 3 doses of the serogroup B meningococcal vaccine VA-MENGOC-BC at 3.5, 5.5 and 7.5 months of age. Immune response pre- and postvaccination was determined by the conventional serum bactericidal assay (SBA), a more sensitive novel whole blood bactericidal assay (WBA) and immunoglobulin ELISA. RESULTS: In 52 and 46% of infants >50% killing of the vaccine serogroup B strain (B:4:P1.19,15) and serogroup C strain, respectively, was demonstrated by the WBA after 2 doses of the vaccine. Serum bactericidal activity (4-fold increase in titer) was induced in only 27% against the vaccine serogroup B strain and in 14% against the serogroup C strain. The changes in WBA and SBA were mirrored by the serogroup B and C immunoglobulin ELISA. Cross-reactive immunogenicity against other (heterologous) serogroup B strains was demonstrated for one of the four further strains assessed by WBA. By age 16 to 18 months SBA, WBA and ELISA responses had declined considerably. The addition of a third dose of vaccine did not appear to significantly influence immunogenicity at 17 months of age. CONCLUSION: The serogroup B outer membrane protein vaccine VA-MENGOC-BC induces a demonstrable immune response in infants against both the serogroup B vaccine strain and against a serogroup C strain. Cross-reactive immunogenicity against other (heterologous) serogroup B strains is limited in this age group.     

Complement-Dependent Bactericidal Activity for E. coli K12 in Serum of Preterm Newborn Infants

ABSTRACT. Complement-dependent serum bactericidal activity for E. coli K12 was assessed in 12 term infants and in 16 preterm infants. In both groups of newborns, at birth, bactericidal reaction by the classical pathway of complement activation was impaired with respect to normal controls at <0.001 level of significance (as estimated by Student's t -test). The serum bactericidal reaction by the alternative pathway of complement activation was significantly impaired only in preterm newborns, being normal in term infants. At a time corresponding to 40 weeks' gestational age also in preterm newborns alternative pathway mediated bactericidal activity for E. coli K12 was found normal. Classical pathway mediated bactericidal activity became normal only at an age corresponding to 52 weeks' gestational age.     

Immunogenicity and reactogenicity of a three-dose primary vaccination course with a combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-haemophilus influenzae type b vaccine coadministered with a meningococcal C conjugate vaccine

AIM: To evaluate the immunogenicity and safety of 3 doses of the combined diphtheria-tetanus toxoids-acellular pertussis-hepatitis B virus-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) vaccine (Infanrix hexa) when coadministered with a CRM197-conjugated meningococcal C vaccine (Meningitec) at different injection sites during the same visit or during separate visits. METHODS: Healthy infants were randomized in an open randomized multicenter study to receive either the DTPa-HBV-IPV/Hib and meningococcal C conjugate vaccines during the same vaccination visit at 2, 4 and 6 months of age (coadministration group) or the DTPa-HBV-IPV/Hib vaccine at 2, 4 and 6 months of age and the meningococcal C conjugate vaccine at 3, 5 and 7 months of age (separate administration group). RESULTS: The immunogenicity analysis included 452 infants, 228 in the coadministration group and 224 in the separate administration group. One month after primary vaccination, 99.1% of subjects in both groups achieved anti-polyribosylribitol phosphate antibody concentrations >/=0.15 microg/mL. The vaccine response against pertussis antigens was at least 99.1% in both groups. For all other DTPa-HBV-IPV/Hib vaccine antigens, at least 97.8% of all subjects of both groups were seroprotected. In addition, 99.5% of all subjects had meningococcal C bactericidal antibody titers >/=1/8 and 99.1% >/=1/128. Coadministration of both vaccines did not result in an increased local or general reactogenicity compared with separate administration. CONCLUSION: Coadministration of the combined DTPa-HBV-IPV/Hib vaccine and the meningococcal C conjugate vaccine during the same vaccination visit was immunogenic and safe.     

Complement-dependent bactericidal activity for E. coli K12 in serum of preterm newborn infants

Complement-dependent serum bactericidal activity for E. coli K12 was assessed in 12 term infants and in 16 preterm infants. In both groups of newborns, at birth, bactericidal reaction by the classical pathway of complement activation was impaired with respect to normal controls at less than 0.001 level of significance (as estimated by Student's t-test). The serum bactericidal reaction by the alternative pathway of complement activation was significantly impaired only in preterm newborns, being normal in term infants. At a time corresponding to 40 weeks' gestational age also in preterm newborns alternative pathway mediated bactericidal activity for E. coli K12 was found normal. Classical pathway mediated bactericidal activity became normal only at an age corresponding to 52 weeks' gestational age.     

Immunologic memory with no detectable bactericidal antibody response to a first dose of meningococcal serogroup C conjugate vaccine at four years

Fourteen children with no detectable bactericidal antibody response to a first dose of meningococcal C conjugate vaccine at 4 years of age were given a booster dose of the same vaccine 2 years later. A rapid 1000-fold rise in postimmunization bactericidal antibody titers, a measured either 7 or 14 days later, suggested previous immunologic priming.     

A new meningococcal conjugate vaccine: What should physicians know and do?

A quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y and W135 (MCV4 [Menactra, sanofi pasteur, Canada]) was introduced in Canada in 2007 for persons two years of age or older. MCV4 adds three serogroups to the meningococcal serogroup C conjugate vaccine, which has been used for several years. The rates of invasive meningococcal serogroup C infection have decreased over the past decade, attributable to the meningococcal C conjugate vaccine. However, the incidence of infection caused by serogroups A, B, Y and W135 have not changed substantially. MCV4 induces the production of protective antibodies to serogroups A, C, Y and W135 in adults and children older than two years of age. Serious adverse events from MCV4 are low. In view of the effectiveness of the meningococcal C conjugate vaccine for young infants and the historic high number of meningococcal serogroup C infections in Canada, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age. MCV4 should also be given to children aged two years who are at increased risk for meningococcal infection. MCV4 may also be considered for HIV-positive children two years of age or older. All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.     

Meningococcal conjugate vaccine in adolescents and children

Disease caused by Neisseria meningitidis is associated with high mortality rates and significant sequelae. Quadrivalent (A, C, Y, W-135) polysaccharide meningococcal vaccine has been available for more than 20 years, and although used widely for adolescents entering college, it has a number of limitations, including short duration of immunity and lack of a herd effect. A quadrivalent meningococcal conjugate vaccine has recently been licensed and endorsed for use in adolescents 11 to 12 years of age, at age 15, or at college entry. Among the key features of the new meningococcal conjugate vaccine are stimulation of both B-cell-dependent and T-cell-dependent immune responses, induction of immunologic memory and booster effects, long-term protection, reduction of nasopharyngeal carriage of N. meningitidis, and herd immunity. Large randomized, double-blind studies in adolescents and 2- to 10-year olds have demonstrated the immunogenicity as well as the safety and tolerability of the new meningococcal conjugate vaccine formulation.     

Immunisation of premature infants

Premature infants are at increased risk of vaccine preventable infections, but audits have shown that their vaccinations are often delayed. Early protection is desirable. While the evidence base for immunisation of preterm infants is limited, the available data support early immunisation without correction for gestational age. For a number of antigens the antibody response to initial doses may be lower than that of term infants, but protective concentrations are often achieved and memory successfully induced. A 2-3-4 month schedule may be preferable for immunisation of preterm infants in order to achieve protection as early as possible, but an additional dose may be required to achieve persistence of protection. This update focuses on the use of routine childhood vaccines in premature infants.     

Immunisation of premature infants.

Premature infants are at increased risk of vaccine preventable infections, but audits have shown that their vaccinations are often delayed. Early protection is desirable. While the evidence base for immunisation of preterm infants is limited, the available data support early immunisation without correction for gestational age. For a number of antigens the antibody response to initial doses may be lower than that of term infants, but protective concentrations are often achieved and memory successfully induced. A 2-3-4 month schedule may be preferable for immunisation of preterm infants in order to achieve protection as early as possible, but an additional dose may be required to achieve persistence of protection. This update focuses on the use of routine childhood vaccines in premature infants.     

Rates of Neisseria meningitidis increasing in young adults

The burden of meningococcal disease has remained unchanged in the United States for the past 4 decades. The currently available meningococcal vaccine is safe and effective, however, due to immunogenic limitations inherent to polysaccharide vaccines, it has been available only for high-risk populations older than 2. Incorporation of a more immunogenic and effective conjugated vaccine into the routine immunization schedule offers an opportunity to substantially affect the incidence of meningococcal disease. The routine use of a meningococcal conjugate vaccine in the United States will save lives and prevent significant morbidity in children and young adults.     

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.