Comparison of diphtheria-tetanus-two component acellular pertussis vaccines in United States and Japanese infants at 2, 4, and 6 months of age.

OBJECTIVE: We compared the diphtheria and tetanus toxoids and bicomponent acellular pertussis vaccine (DTaP) responses in Japanese and United States infants. DESIGN: This was a double-blind, comparative study. SETTING: Private pediatric practices in Japan and the U.S. participated. SUBJECTS: One hundred eighty-nine healthy 2-month old infants were tested. INTERVENTIONS: Infants were immunized at 2, 4, and 6 months of age. The Japanese formulation (DTaP-J) contained 20 micrograms of pertussis toxin (PT) and 20 micrograms of filamentous hemagglutinin (FHA); the U.S. formulation (DTaP-US) contained 23.4 micrograms of each antigen. Parents used a standard form to record average adverse experiences. Serum was obtained before the first immunization, 2 months after the second immunization, and 1 month after the third immunization. MEASUREMENTS: Differences in DTaP-J and DTaP-US were evaluated in Japanese infants immunized subcutaneously (s.c.). Differences due to ethnicity and to route of administration were compared in U.S. infants immunized with DTaP-US s.c. or intramuscularly (i.m.). An indirect enzyme-linked immunosorbent assay was used to determine immunoglobulin G antibody responses to PT, FHA, and tetanus toxoid. Neutralizing antibody to PT was measured by a Chinese hamster ovary call assay. Diphtheria antitoxin was assayed by serum neutralization on VERO cells. RESULTS: Statistical differences (P < .05) in adverse events included less fatigue after immunization with DTaP-US compared with DTaP-J. Erythema of more than 2.5 cm was more frequent, but erythema less than 2.5 cm was less frequent in Japanese infants compared with U.S. infants. Fewer Japanese infants were febrile ( > 38 degrees C), tired, or irritable. Subcutaneous immunization resulted in a greater frequency of erythema and induration. The DTaP-US resulted in an equivalent response to PT and a greater response to FHA. More Japanese infants demonstrated at least a fourfold response over preimmunization antibody values to FHA. In U.S. infants, antibody responses to the contained pertussis antigens were equivalent after i.m. and s.c. administration. Compared with Japanese infants receiving DTaP-J s.c., U.S. infants receiving DTaP-US i.m. had equivalent responses to PT and a greater response to FHA. CONCLUSIONS: United States infants receiving an i.m. injection of a U.S. -produced bicomponent DTaP vaccine produced antibody responses to the contained pertussis antigens at least equal to those of Japanese infants receiving a similar bicomponent DTaP vaccine shown to be effective in older Japanese children.

Comparison of the safety and immunogenicity of acellular (BIKEN) and whole-cell pertussis vaccines in 15- to 20-month-old children.

OBJECTIVE: To compare the immunogenicity and reactogenicity of a two-component acellular pertussis vaccine (BIKEN) with whole-cell diphtheria and tetanus toxoids and pertussis vaccine (WC-DTP) when administered to children aged 15 to 20 months. DESIGN: A randomized, double-blind study. SETTING: Children in this study were from 12 general pediatric practices (11 were private and one was university-affiliated) and one inner-city university pediatric clinic. PARTICIPANTS: Two hundred forty-six children aged 15 to 20 months who had received a three-dose primary series of standard WC-DTP vaccine during infancy. SELECTION PROCEDURES: Children were randomly assigned to receive either WC-DTP or one of three lots of acellular diphtheria and tetanus toxoids and pertussis vaccine (DT-aP) in a 1:3 ratio at the 11 private practices and in a 1:1 ratio at the university-affiliated practice and inner-city university pediatric clinic. INTERVENTIONS: The DT-aP vaccines contained 23.4 micrograms each of pertussis toxin and filamentous hemagglutinin per 0.5 mL and the same concentrations of diphtheria and tetanus toxoids as WC-DTP. Serum samples were obtained on the day of immunization and 4 to 6 weeks later. Adverse reactions at 6, 24, 48, and 72 hours were recorded by parents who were contacted by telephone at 24 and 72 hours and 14 days after immunization. MEASUREMENTS/MAIN RESULTS: An indirect enzyme-linked immunosorbent assay method was used to determine IgG antibody response to pertussis toxin and filamentous hemagglutinin and IgG, IgA, and IgM to tetanus toxoids; a Chinese hamster ovary cell assay was used to measure functional antibodies to pertussis toxin; serum neutralization on VERO cells assayed diphtheria anti-toxin. Recipients of the DT-aP vaccine had fewer local reactions in the first 6 to 48 hours and fewer systemic reactions at 24 hours than did recipients of the WC-DTP vaccine. Acetaminophen was administered to 31% of DT-aP recipients compared with 63% of WC-DTP recipients. Infants given DT-aP had higher geometric mean antibody titer levels against pertussis antigens after vaccination. CONCLUSION: The BIKEN DT-aP vaccine used in this study is less reactogenic and more immunogenic for selected pertussis antigens than the WC-DTP vaccine in children aged 15 to 20 months.