The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Abstract

BackgroundCombination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.Methods299 healthy infants were randomised to receive either DTPw-HBV/Hib2.5 [Kft] DTPw-HBV/Hib2.5 or DTPw-HBV/Hib according to the 6-10-14 week EPI schedule. Blood samples were analysed prior to the first dose of study vaccine and one month after the third vaccine dose for the analysis of immune responses. Solicited local and general symptoms such as pain, redness and swelling at the injection site and drowsiness and fever, unsolicited symptoms (defined as any additional adverse event) and serious adverse events (SAEs) were recorded up to 20 weeks of age.ResultsOne month after the third vaccine dose, 100% of subjects receiving DTPw-HBV/Hib2.5 [Kft] or DTPw-HBV/Hib and 98.8% of subjects receiving DTPw-HBV/Hib2.5 vaccine had seroprotective levels of anti-PRP antibodies (defined as anti-PRP antibody concentration ≥0.15 μg/ml). Seroprotective antibody concentrations were attained in over 98.9% of subjects for diphtheria, tetanus and hepatitis B. The vaccine response rate to pertussis antigen was at least 97.8% in each group. Overall, the DTPw-HBV/Hib2.5 [Kft] vaccine was well tolerated in healthy infants; no SAEs were reported in any group.ConclusionsThe DTPw-HBV/Hib2.5 [Kft] vaccine was immunogenic and well-tolerated when administered according to the EPI schedule to Indian infants.Trial registrationhttp://www.clinicaltrials.gov NCT00473668

Primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in infants in Mali and Nigeria: a randomized controlled trial

“…Antibody concentrations against the PRP, tetanus and diphtheria antigens were higher when PHiD-CV was co-administered, presumably due to enhancement of these immune responses by the tetanus toxoid and diphtheria toxoid carrier proteins used for serotypes 18C and 19F, respectively, in PHiD-CV [28]. High antibody GMCs and seroprotection rates were however observed for these antigens in both groups, including the PRP antigen, confirming the good immunogenicity of a reduced PRP content Hib vaccine (2.5 μg of PRP) compared to the more usual 10 μg PRP vaccines [41-45]. …”

A phase III single arm, multicenter, open-label study to assess the immunogenicity and tolerability of a pentavalent DTwP–HepB–Hib vaccine in indian infants

“…Safety data from these studies showed pain, swelling and erythema as the most commonly reported solicited local reactions, and most frequently reported solicited systemic reactions were fever and irritability comparable with our observations. [12][13][14][15][16][17] For several decades, inactivated whole-cell pertussis vaccines (wP) have been part of national childhood vaccination programs, dramatically reducing the considerable public health impact of pertussis. 18 In most emerging and developing countries, DTP vaccination in infants.…”

“…Although direct comparisons are not possible due to differences in data collection and analysis methods, seroprotection/seroconversion rates and reactogenicity profile were found to be similar to other pentavalent vaccines studied in Indian infants. [12][13][14][15][16][17] This study was designed to assess immunogenicity in terms of accepted seroprotection or seroconversion criteria against all five vaccine antigens one month after the third vaccination, and safety and tolerability after each vaccine dose. The study was conducted according to Good Clinical Practice and in accordance with the Ethical Guidelines for Biomedical Research on Human Subjects and Declaration of Helsinki.…”

Comparison of the immunogenicity and safety of pentavalent vaccine Quinvaxem in a compact prefilled auto-disabled (cPAD) injection system versus single-dose vials in healthy infants: a phase 3, open-label, randomized, parallel-group, non-inferiority study

“…[27][28][29] However, the safety and immunogenicity of two different presentations of Quinvaxem had not been studied to date. In this study, the seroconversion/seroprotection rates were similar in the cPAD and single-dose vial groups.…”

“…Frequent, but usually mild adverse reactions, and a fear of rare but serious acute or chronic neurological events associated with wP vaccination, prompted the development of a new generation of pertussis vaccines, the aP vaccines, which are believed to have fewer such reactions than wP vaccines. 27,32 However, evidence suggests that licensed aP vaccines have lower initial efficacy, faster waning of immunity, and possibly a reduced impact on transmission compared with current internationally available wP vaccines. 33,34 Mathematical modeling studies and baboon models support the hypothesis that transition from wP to shorter duration of protection aP may be associated with disease resurgence.…”