Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations

Abstract

Mixing DTaP and Hib vaccines for primary immunization caused a decrease in anti-Hib antibody response, although after primary immunization as after booster doses, all subjects showed antibody concentrations considered to be protective for invasive Hib disease. Mixing of the vaccines did not result in increased reactogenicity.

Immunologic response to Hib tetanus toxoid conjugated vaccine coadministered with DTPa either mixed or in two separate injections in toddlers not primed with Hib vaccine

“…In several studies irrespective of whether the vaccine was used for primary or booster dosing, the combination of DTPa/Hib in one syringe has resulted in significantly lower anti-PRP antibody titres as compared to separate administration of DTPa and Hib components. [1][2][3] Similar lower anti PRP responses were also seen in this study on Day 7 after immunization but one month later such differences had disappeared. However, the difference on Day 7 might have been influenced by the limited number of subjects studied.…”

“…15,16 The interesting findings here were much higher than in previous studies anti-TT and anti-PRP antibody titres (40.632 IU/ml vs 24.949 IU/ml and 47.158 mg/ml vs 78.36 mg/ ml after combined and separate administration, respectively) in the population primed with TT but not with Hib vaccine. 3,12,15 The latter contrasts to (previous report by Eskola et al ref. 4) who showed that in unimmunized children a single dose of Hib induced antibody levels of 1.0-10.0 mg/ml whereas in previously immunized children booster responses to HbOC, PRP-D and PRP-T were in range of 20.0 to 60.0 mg/ml.…”

“…Furthermore, in countries such as Germany where the combined DTPa/Hib vaccine has been implemented into national immunization program, no increase in the incidence of Hib infections in comparison with time when Hib was given as a separate injection has occurred. 11 Another interesting finding described also in some previous studies [1][2][3]12 was a significantly lower and most likely clinically irrelevant antibody response to TT after combined administration of DTPa and Hib as compared with separate administration. Reasons and mechanisms of such interference have been extensively studied in animal models and showed that suppression of PRP is a plausible result of interaction between the Hib and TT components.…”

“…However, decreased antibody response has been reported to the H. influenzae (Hib) polyribosylribitol phosphate conjugated to the tetanus toxoid (PRP-T) and oligosaccharide-Hib conjugate conjugated to CRM197 (HbOC) when this was administered in a single injection with diphtheria-tetanus-acellular pertussis (DTPa). [1][2][3][4] The factors leading to such immune interferences have been suggested to be associated with the vaccine content (e.g., interaction between different antigens, adjuvants, reconstitution), with the trial design and/or with the subject's characteristics (e.g., immune memory, ethnicity). It has been demonstrated that children who received their first Hib dose with PRP-D or HbOC vaccines in the second year of life achieved lower antibody levels than those who have been primed in infancy.…”

Combination vaccines in the South African setting

“…These rates may seem higher as the adverse events seem to mimic the sum total of adverse event rates for each individual antigen used [35][36][37] but may even have lower rates [11]. However, the reduction in amount of vaccine preparations will lead to decrease in cumulative exposure to stabilizers and preservatives contained in vaccines [35,38], a benefit well worth considering.…”