A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial

Abstract

NCT00258700. Study ID: 103974 (http://clinicaltrials.gov).

Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines – Exploratory Analyses within a Randomised Controlled Trial

“…The differences between vaccines in induction of MenC-specific memory B-cells may explain the differential antibody response noted following primary and booster vaccines when children were primed with either a MenC-CRM 197 vaccine or Hib-MenC-TT in the first year of life and given a Hib-MenC-TT booster as toddlers [8], [9]. In these earlier studies, children in the MenC-CRM 197 primed groups had higher SBA titres one month after primary vaccines, but lower SBA titres one month after the Hib-MenC-TT booster, than children in the Hib-MenC-TT primed groups.…”

“…In the context of waning bactericidal antibody described in the first year of life following infant immunizations [8], [30], an increase in the number of MenC-specific memory B-cells between 5 and 12 months of age suggests that after primary MenC vaccines, memory B-cells continue to be generated for several months, but there is a decline in the proportion that differentiate into plasma cells. Despite waning of bactericidal antibody levels, antibody avidity has also been shown to increase following primary immunisations with MenC and pneumococcal conjugate vaccines in infants, until 12 months of age [11], [31].…”

“…Furthermore, higher serum bactericidal assay (SBA) titres were observed following Haemophilus influenzae type b (Hib) and MenC conjugate (Hib-MenC-TT) booster in children primed with Hib-MenC-TT than children primed with monovalent MenC-CRM 197 in the first year of life, even though post-primary immunisation SBA titres were lower in the former group [8], [9]. These findings may relate to differences in the ability of these vaccines to generate memory B-cells following primary immunisations.…”

Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo®) in the context of treatment and prevention of invasive disease

“…Insufficient published data exist to determine whether carrier proteins have a meaningful impact on the clinical efficacy of meningococcal vaccines 49,70,71. A recent study in toddlers who received a booster dose of combined Haemophilus influenzae type B and meningococcal serogroup C vaccine employing a tetanus toxoid protein carrier indicated that boosting was superior among children primed with tetanus toxoid-containing vaccines 72,73. Similar studies have not been performed for CRM conjugate vaccines.…”

A Randomized, Controlled Trial to Assess the Immunogenicity and Safety of a Heptavalent Diphtheria, Tetanus, Pertussis, Hepatitis B, Poliomyelitis, Hib and Meningococcal Serogroup C Combination Vaccine Administered at 2, 3, 4 and 12–18 Months of Age

“…these results are in line with previous studies showing that high anti-pRp concentrations are induced when Hib antigens are combined with Menctt antigens (eg, Hib-Menc-tt vaccine). [25][26][27][28] this suggests a potential positive interference of the Menc-tt antigen on the Hib response through their common carrier or by another mechanism. alternatively, the higher Hib response could be explained by a reduction of immune interferences that have been observed in Dtpa-Hib combination vaccines.…”