A new DTPw-HBV/Hib vaccine: Immune memory after primary vaccination and booster dosing in the second year of life

Abstract

The response to booster vaccination at 15-18 months of age and the presence of immune memory in 10-month old children, primed with a new combined diphtheria-tetanus-hepatitis B-whole cell pertussis vaccine extemporaneously mixed with Haemophilus influenzae type b-tetanus toxoid conjugate (DTPw-HBV/Hib) from new antigen sources and containing 2.5 microg polyribosyl-ribitol-phosphate (PRP) was assessed. Primary vaccination with the new DTPw-HBV/Hib vaccine was immunogenic and of comparable tolerability to commercially available Tritanrix HepB/Hiberix. Children were boosted with DTPw-HBV, DTPw-HBV/Hib or separate DTPw-HBV+Hiberix. Immune memory was assessed through administration of 10 microg PRP polysaccharide. Anti-PRP antibody GMCs increased substantially after the challenge in DTPw-HBV/Hib-primed subjects indicating the presence of immune memory. One month after the booster dose, 100% of subjects had seroprotective antibody concentrations against PRP, diphtheria and tetanus, >95% were seroprotected against hepatitis B, > or =94.0% had a pertussis booster response. Substantial increases in antibody GMCs against all antigens were observed. Swelling >20 mm was the most common Grade 3 solicited symptom reported (up to 26.0% of subjects). Fever >39.5 degrees C was uncommon (>2.5%). Eleven large swelling reactions were reported; none involved an adjacent joint. One serious adverse event occurred that was considered unrelated to vaccination. This new DTPw-HBV/Hib vaccine with new vaccine components and 2.5 microg PRP induced effective priming against Hib evidenced by a vigorous anamnestic response on exposure to PRP polysaccharide. The booster dose was immunogenic and the safety profile was acceptable. Combined DTPw-HBV and DTPw-HBV/Hib vaccines using new vaccine antigen sources will promote continued supply of combined DTPw-based vaccines to global mass vaccination campaigns.

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

“…However, the anti-PRP GMC point estimate for the comparator DTPw-HB/Hib 2.5 vaccine (which, unlike the other 2 vaccines [ Tritanrix (tm)-HepB/ Hiberix (tm) and Zilbrix -Hib(tm)] used in this study, is not a WHO pre-qualified) vaccine [17,18] was significantly lower than for the full-content DTPw-HB/Hib. The results from this study agree with previous findings from the Philippines and Latina comparing a DTPw-HB/Hib 2.5 vaccine with the licensed vaccine [6,19] and support the observation that vaccines containing reduced amounts of PRP-tetanus toxoid conjugate generate effective antibody responses and immunological protection [16,7,20-26]. The responses to the other antigens of DTPw-HBV/Hib 2.5 [Kft] were also found to be within similar 95% confidence intervals as the other vaccines, in terms of seroprotection and vaccine response, further substantiating the non-inferiority of the DTPw-HBV/Hib 2.5 [Kft] vaccine to the two comparator vaccines.…”

A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzaetype b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers

“…The rate of local and general adverse events in this study is consistent with published data following DTPw booster vaccination 9 , 10 . Five subjects experienced febrile convulsion after vaccination.…”

Immunogenicity, reactogenicity and safety of three-dose primary and booster vaccination with combined diphtheria-tetanus-whole-cell pertussis-hepatitis B-reduced antigen contentHaemophilus influenzaetype b vaccine in Filipino children

“…The results are in line with previous studies of DTPw-HBV/Hib-low dose vaccines that showed good immunogenicity and anamnestic responses when infants were primed with Hib-TT conjugate vaccines containing reduced PRP. [21][22][23][24] The immune response in terms of seroprotection rates for diphtheria and tetanus was similar in both study groups one month after primary vaccination, while the percentage of subjects with seroprotective anti-HBs antibody concentrations and vaccine response to pertussis was significantly higher in the DTPw-HBV LT /Hib 2.5 group (non-overlapping 95% CIs). Thus, the lowering of thiomersal content did not have any adverse influence on the immunogenicity of the hepatitis and pertussis components of the combined vaccine.…”