Evaluation of the induction of immune memory following infant immunisation with serogroup C Neisseria meningitidis conjugate vaccines--exploratory analyses within a randomised controlled trial

Abstract

Aim: We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory.

Methods: Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age.

Results: Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children.

Conclusions: MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.

Trial registration: EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.

Conflict of interest statement

Competing Interests: This study has received part-funding from a commercial source. Funding was received from GlaxoSmithKline Biologicals, Rixensart, Belgium. AJP and MDS act as chief or principal investigators for clinical trials conducted by the University of Oxford, sponsored by vaccine manufacturers, but receive no personal payments from them. MDS has participated in advisory boards and industry sponsored symposium for vaccine manufacturers, but receives no personal payments for this work. AK and MDS have received financial assistance from vaccine manufacturers to attend conferences. One of the vaccines included in the study [Hib-MenC-TT (MenitorixTM, GlaxoSmithKline Biologicals, Rixensart, Belgium)] is produced by GlaxoSmithKline. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials and the authors have no competing interests with respect to the findings of this report.

Figures

Figure 1. Number of children enrolled and included in the final analysis for MenC-specific memory B-cells.

Figure 2. Schedule of study visits and procedures, including vaccines administered and timing of blood draws used to measure MenC-specific memory B-cells.

Figure 3. Number of MenC-specific memory B-cells (log10 scale) detected in the peripheral blood of individual participants after immunisation with different schedules of MenC conjugate vaccines, at each time-point following infant primary and booster vaccines.

Figure 4. Number of MenC-specific memory B-cells detected in the peripheral blood of infants 6 days after a Hib-MenC-TT booster at 12 months of age, according to different primary immunisation schedules (magnified from Figure 3 ).

Figure 5. Kinetics of the number of antigen-specific memory B-cells detected in the peripheral blood of infants after immunisation with different schedules of MenC conjugate vaccines, at each time-point following primary and booster vaccines, based on geometric mean concentrations for each study group at each visit.