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

PLoS One. 2014 Jul 14;9(7):e101672. doi: 10.1371/journal.pone.0101672. eCollection 2014.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology
  • Bacterial Vaccines / immunology*
  • Female
  • Humans
  • Immunologic Memory*
  • Infant
  • Male
  • Neisseria meningitidis, Serogroup C / immunology*
  • Vaccination
  • Vaccines, Conjugate / immunology

Substances

  • Bacterial Vaccines
  • Vaccines, Conjugate

Associated data

  • ClinicalTrials.gov/NCT01129518

Grants and funding

This study was sponsored by the University of Oxford. Funding was received from the NIHR Oxford Biomedical Research Centre, GlaxoSmithKline Biologicals, Rixensart, Belgium, and the European Society for Pediatric Infectious Diseases. 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. Funding from the NIHR Biomedical Research Centre Programme through the Oxford Partnership Comprehensive Biomedical Research Centre provides support to the Oxford Vaccine Group, including salary support for AK and MDS. AJP is a Jenner Investigator and James Martin Senior Fellow. AK was a James Martin Fellow and has received funding from the James Martin Vaccine Design Institute. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.