Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

Abstract

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by BioManguinhos and Instituto Butantan (DTP/Hib-BM) Key words: vaccines -immunization -combination vaccines -DTP/Hib vaccineThe combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTP/Hib) vaccine allows for a reduction in the number of required injections, thus improving compliance to the vaccination schedule and higher vaccination coverage. Moreover, the combined vaccine has reduced the logistical costs related to factors such as number of visits to health care centers, number of syringes and needles required and necessary storage space.In 1998, a technological transfer agreement was established with GlaxoSmithKline (GSK) for the Brazilian production of Hib vaccine (Homma et al. 2005). In 1999, Hib vaccine produced by GSK was introduced in the Brazilian National Immunization Program (NIP) and administered at two, four and six months of age, concomitant to the administration at another site of a DTP vaccine produced by Instituto Butantan. Since 2002, these vaccinations have been administered as a single Reports on the quality, immunogenicity and safety of this combination have been demonstrated in a clinical study (Clemens et al. 2003).The technology transfer from GSK to Bio-Manguinhos (BM) was a strategic step toward the routine availability of this vaccine by the NIP. This process was concluded in 2005 with the production of the conjugate Hib vaccine by BM.The present study aimed to determine if the quadrivalent vaccine with the Hib component produced by BM (DTP/Hib-BM) had immunogenicity and reactogenicity similar to that of the Hib vaccine produced by GSK (DTP/Hib-GSK). This was a study for clinical validation of the DTP/Hib-BM vaccine, which was required for its licensure by the Brazilian National Regulatory Agency. The performance of this combined vaccine is extremely important considering its role in the containment of the target diseases and its well-known reactogenicity accounted for by the whole-cell pertussis component.The combined DTP/Hib vaccine with a cellular pertussis component generally provides good efficacy for all antigens, but in some studies the combination resulted in decreased immunogenicity of the Hib component in comparison to individual administration. Despite this finding, antibody levels against the vaccination com-

Prevalência e fatores associados à ocorrência de eventos adversos pós-vacinação em crianças

“…The combination of vaccines enables a reduction of operational and logistic costs and provides a higher level of comfort to users (displacements to health units, number of injections applied, and reduction in the occurrence of local manifestations associated with less exposure). (1,18) These aspects may contribute to increase adherence to immunization.…”

Pattern of functional antibody activity against Haemophilus influenzae type b (Hib) in infants immunized with diphtheria-tetanus-pertussis/Hib Brazilian combination vaccine

“…Regarding the Hib component, there was 100% seroprotection (≥0.15 μg/mL), and there was no clinically relevant difference in reactogenicity between the 3 lots of Brazilian DTP/Hib studied and the reference vaccine lot with Hib produced by GSK (17).…”

“…This study is a follow-up of a previously reported clinical trial in which the immunogenicity, reactivity and consistency of production of DTP/Hib-BM was assessed (17). One thousand infants were immunized according to the immunization program of the Brazilian Health Ministry in a double-blind and randomized study approved by the National Research Ethics Committee, the Ethics Committee of Fundação Oswaldo Cruz and of the Municipal Health Secretary of Rio de Janeiro, and by the National Regulatory Agency.…”

“…One thousand infants were immunized according to the immunization program of the Brazilian Health Ministry in a double-blind and randomized study approved by the National Research Ethics Committee, the Ethics Committee of Fundação Oswaldo Cruz and of the Municipal Health Secretary of Rio de Janeiro, and by the National Regulatory Agency. The protocol was registered under Standard Randomized Clinical Trial Number 67676353 (17).…”

Evaluation of the immunogenicity and safety of an indigenously developed DTwP-Hib tetravalent combination vaccine (Shan 4) with EasyFourTM in Indian infants administered per EPI schedule

“…[8][9][10] In developing countries, however, the experience with conjugate Hib vaccines is limited and complicated by the fact that the vaccines are administered in two vaccination schedules. Studies from the Brazil, 11 Gambia 12,13 and Chile 14,15 where the vaccine was administered to children from the age of 2 months show the vaccines to be immunogenic and protective against Hib disease. The data is even more limited for the vaccines being administered at 6, 10 and 14 weeks, the current World Health Organization (WHO) Expanded Programme on Immunization (EPl) schedule of vaccination.…”