John Thipphawong

Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis-Haemophilus b conjugate vaccine administered to infants at two, four and six months of age

Safety, immunogenicity and lot consistency of five-component pertussis combination vaccine (CPDT-IPV//PRP-T) in infants were compared to that of whole cell pertussis combination vaccine (DPT-IPV//PRP-T), as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV//PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in antibody responses were observed between lots of component pertussis vaccine. Higher concentrations of diphtheria and tetanus antitoxins were induced by separate than by combined injection of CPDT-IPV and PRP-T, but no other differences in immunogenicity were observed. Adverse reactions were more than twice as frequent after whole cell than after component pertussis vaccines. Antibody responses to pertussis toxoid, filamentous hemagglutin and pertactin were significantly greater after component vaccines, while the response to type 3 poliovirus was higher after whole cell vaccine. No significant differences were observed for other vaccine components. CPDT-IPV//PRP-T was safe and immunogenic in infants. Antibody results were similar to those observed in a Swedish field trial that demonstrated CPDT to be 85% effective in preventing clinical pertussis.

An evaluation of the safety and immunogenicity of a five-component acellular pertussis, diphtheria, and tetanus toxoid vaccine (DTaP) when combined with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (PRP-T) in Taiwanese infants

Objective. Immunologic interference particular to the Haemophilus influenzae type b (Hib) response has been observed with previous acellular pertussis-Hib combination vaccines. To test this hypothesis a clinical trial to assess the safety and immunogenicity of a five-component (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) when given simultaneously with a lyophilized Hib-tetanus toxoid conjugate vaccine (PRP-T) in infants at 2, 4, 6, and 18 months of age was conducted. The study compared two methods of administration: both vaccines combined in a single syringe and administered as a single injection, or both vaccines administered concurrently but at separate sites of injection. Methods. Healthy 2-month-old infants were enrolled at the National Taiwan University Hospital. DTaP, PRP-T, and oral poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction information was collected by telephone 2 days after each vaccination. Serum was collected at 2, 6, 7, 18, and 19 months of age. Results. One hundred thirty-five healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18-month booster: 68 received the combined vaccine and 67 the separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were reported. Serologic responses were comparable between the groups. Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7 months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN (100 vs 77), and FIM (922 vs 702). At 19 months, pertussis results were, for combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197), and FIM (892 vs 732). Only the 7-month PT response in the combined group was significantly higher (combined 131 EU/mL vs separate 105 EU/mL). After the third dose (age 6 months), all subjects achieved serologic serum antibody levels indicative of protection against Hib, diphtheria, tetanus, and poliovirus types 1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of protection (≥0.15 μg/mL) against Hib after only two doses. At 7 months, anti-PRP geometric mean titer values were 11.8 μg/mL in the combined group compared with 13.0 μg/mL in the separate group. The anti-PRP geometric mean titers after the 18-month booster were 58.5 μg/mL in the combined group versus 55.3 μg/mL in the separate group. Conclusion. The five-component DTaP vaccine may be combined with PRP-T vaccine without clinically significant immunologic interaction when given in a 2-, 4-, 6-, and 18-month schedule.

Measles vaccination of infants in a well-vaccinated population.

During outbreaks of measles, measles vaccine is recommended for infants considered to be at risk who are 6 months of age and older. In a prospective trial the serologic response to early measles immunization has been evaluated in 125 infants given monovalent measles vaccine at 6 to 8.5 months of age and measles‐mumps‐rubella at 15 months. The response to vaccination was measured by plaque reduction neutralization (PRN) assay and enzyme immunoassay. Infants were grouped by the mothers immunization history: natural immunity (n = 60, Group 1); killed followed by live, further attenuated vaccine (n = 22, Group 2); and live, further attenuated vaccine only (n = 43, Group 3). The prevaccination geometric mean titer (GMT) by PRN for Group 1 (GMT = 69) was significantly higher than that of Group 2 (GMT = 18) or 3 (GMT = 13). Seroconversion (4‐fold increase in PRN titer) rates after monovalent vaccine were 31,71 and 76% for Groups 1,2 and 3, respectively. Seroconversion percentages were higher when measured 6 to 8 weeks after vaccination compared with 4 to 5 weeks. After measles‐mumps‐rubella ≥97% of all infants had PRN titers >120 and were measles IgG‐positive by enzyme immunoassay. These data show that as demographics shift to a well‐vaccinated maternal population and susceptibility in younger infants, measles vaccination before the currently recommended age will be effective.

Evaluation of booster doses of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine in 18-month-old children

A booster dose of Haemophilus influenzae type b conjugate vaccine in the second year of life is the final step in the recommended series of doses to protect infants from invasive infection. This study assessed the safety and immunogenicity of PRP-T conjugate vaccine booster doses (Act-HIB, Connaught Laboratories Ltd). The participants were 367 healthy children who had taken part in a study of primary immunization with PRP-T. At 18-19 months old, subjects were randomly assigned to receive diphtheria-pertussis-tetanus (DPT) and PRP-T vaccines either mixed in one syringe (n = 183) or separately in opposite limbs (n = 184). Adverse events were monitored for 48 h after immunization. Blood was obtained prior to vaccination in half of the subjects (combined injections group) and following vaccination in all subjects to test for antibodies to each of the antigens administered. Local adverse reactions were infrequent with PRP-T alone and equally frequent at sites of DPT or DPT/PRP-T injection, except for redness > or = 25 mm in diameter which was more frequent after the combined vaccines (25.1 versus 14.1%, p < 0.01). Systemic adverse events did not differ in type or frequency between groups. Before immunization, the geometric mean anti-PRP level in those tested was 0.41 micrograms ml-1; 26.7% had levels below 0.15 micrograms ml-1. Both treatment groups responded strongly to vaccination. In those serially tested, anti-PRP levels rose by over 90-fold, to 38.1 micrograms ml-1.(ABSTRACT TRUNCATED AT 250 WORDS)

COMPARATIVE IMMUNOGENICITY OF AN ACELLULAR PERTUSSIS -INACTIVATED POLIO(DTaP-IPV) VACCINE USED TO RECONSTITUTE LYOPHILIZED H. INFLUENZAE B (PRP-T) OR LICENSED DTwP-IPV-PRP-T VACCINE IN INFANTS † 743

Recent attempts to combine DTaP, HIB and IPV have been hindered by significant interactions particularily to the HIB component. We conducted a randomized, controlled trial to compare two pentavalent vaccines in infants aged 2, 4 and 6 months. The acellular pertussis (aP) vaccine was the five component vaccine containing Pertussis Toxoid (PT), Filamentous Haemagglutinin(FHA), Fimbrae 2&3 (FIM), Pertactin (69kDa) which was demonstrated to have 85% efficacy in a Swedish efficacy trial. This acellular pertussis combination, DTaP-IPV//PRP-T, produced excellent responses to all antigens with no clinically significant interactions. Antibody levels to the two pentavalent vaccines at 7 months of age (1 month after dose 3) are below. HIB responses were identical whether the PRP-T was given combined with DTaP-IPV(GMT=4.40) or given separately from DTaP-IPV (GMT=3.83).Table