Vaccine antigen interactions after a combination diphtheria-tetanus toxoid-acellular pertussis/purified capsular polysaccharide of Haemophilus influenzae type b-tetanus toxoid vaccine in two-, four- and six-month-old infants.
OBJECTIVE
The safety and immunogenicity of a diphtheria-tetanus toxoid-acellular pertussis vaccine (DTaP; Trepedia)/Haemophilus influenzae b polysaccharide (PRP-T; ActHib) combined vaccine (TriHibir; Pasteur Mérieux Connaught) was compared with DTaP and PRP-T given at the same visit but at separate sites in a prospective multicenter, open label trial.


METHODS
Infants were randomized to four groups (three consistency lots of DTaP/PRP-T vs. one of the consistency lots given as separate vaccines); injections were administered at 2, 4 and 6 months of age. Pre-Dose 1 and post-Dose 3 sera were assayed for antibody titers against all antigens. Reactions to the vaccinations were assessed by parent questionnaire for 30 days after each injection visit.


RESULTS
Four hundred eighty-five infants were enrolled; 296 evaluable infants were included in the DTaP/PRP-T group compared with 70 infants in the DTaP and PRP-T vaccine group. Infants who received the combined vaccine had higher post-Dose 3 geometric mean antibody titers to diphtheria antitoxin (P < 0.01) and pertussis filamentous hemagglutinin (P < 0.05) and lower geometric mean antibody titers to tetanus antitoxin (P < 0.05) and Haemophilus influenzae b (Hib) polysaccharide (PRP) (P < 0.05). The geometric mean anti-PRP antibody titer in the DTaP/PRP-T group was 4.3 micrograms/ml compared with 7.0 micrograms/ml in the separate vaccine group (P < 0.05), and the percentage of infants with antibody titers > or = 0.15 and 1 microgram/ml were, respectively, 95 and 86%, whereas they were 100% for both titers in the separate vaccines group. DTaP/ PRP-T vaccine given concomitantly or 1 month apart from hepatitis B vaccine and oral poliomyelitis vaccine caused no significant differences in immunogenicity or safety. The safety assessments for the DTaP/PRP-T vaccine showed no consistent differences in systemic or local injection site reactions compared with DTaP and PRP-T administered separately.


CONCLUSIONS
Although the antibody responses to tetanus and Hib polysaccharide in the evaluated DTaP/PRP-T combined vaccine were significantly lower than those seen after separate DTaP and PRP-T administration, the combined vaccine elicited an immune response against diphtheria, tetanus, pertussis and Haemophilus influenzae b likely to confer protection.
Pichichero
M E
ME
University of Rochester, Elmwood Pediatrics, NY, USA. mepo@uhura.cc.rochester.edu
Latiolais
T
T
Bernstein
D I
DI
Hosbach
P
P
Christian
E
E
Vidor
E
E
Meschievitz
C
C
Daum
R S
RS
D000704:Analysis of Variance; D000942:Antigens, Bacterial / Q000032:analysis / Q000276:immunology*; D016009:Chi-Square Distribution; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000276:immunology; D004347:Drug Interactions; D005260:Female; D005500:Follow-Up Studies; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D017325:Hepatitis B Vaccines / Q000494:pharmacology; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D011055:Poliovirus Vaccine, Oral / Q000494:pharmacology; D011446:Prospective Studies; D013745:Tetanus Toxoid / Q000008:administration & dosage* / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage* / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage*
D000942:Antigens, Bacterial; D004168:Diphtheria Toxoid; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D017325:Hepatitis B Vaccines; D011055:Poliovirus Vaccine, Oral; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate