Related Experiment Videos
Memory B cell response to a PCV-13 booster in 3.5year old children primed with either PCV-7 or PCV-13
Johannes Trück1, Amber Thompson1, Begonia Morales-Aza2
1Oxford Vaccine Group, Department of Paediatrics, University of Oxford and the NIHR Oxford Biomedical Research Centre, Oxford, UK.
Insights
Pneumococcal conjugate vaccines (PCV) prime children for immune memory. Prior PCV-13 vaccination, compared to PCV-7, showed higher initial memory B cells (BMEM) for specific serotypes, but responses equalized after a PCV-13 booster.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Pneumococcal protein-polysaccharide conjugate vaccines (PCV) induce protective antibodies and immunological memory.
- Memory B cells (BMEM) are crucial for rapid secondary antibody responses and long-term antibody persistence after vaccination.
- Previous studies compared infant immunization with 7-valent (PCV-7) and 13-valent (PCV-13) vaccines.
Purpose of the Study:
- To investigate if prior pneumococcal conjugate vaccine priming influences BMEM responses in children.
- To compare BMEM responses after a PCV-13 booster in children previously primed with PCV-7 versus PCV-13.
Main Methods:
- Recruited 3.5-year-old children from a prior PCV-7 vs. PCV-13 trial.
- Collected blood samples before and 1 month after a PCV-13 booster.
- Quantified serotype-specific BMEM using cultured ELISpot assay and correlated with IgG concentrations and opsonophagocytic activity (OPA) titers.
Main Results:
- Baseline BMEM frequencies were low but higher for serotypes 14 and 3 in PCV-13 primed children.
- Following PCV-13 booster, BMEM frequencies increased and were similar between groups for all tested serotypes.
- A significant inverse correlation between baseline antibody concentrations/OPA titers and post-booster BMEM was observed for serotype 3, suggesting antibody-mediated inhibition of BMEM formation.
Conclusions:
- Prior PCV-13 priming may enhance initial BMEM for certain serotypes compared to PCV-7.
- Booster vaccination with PCV-13 elicits comparable BMEM responses regardless of prior priming history.
- Pre-existing antibodies against Streptococcus pneumoniae serotype 3 may inhibit BMEM generation upon booster vaccination.
Abstract:
Pneumococcal protein-polysaccharide conjugate vaccines provide direct protection against Streptococcus pneumoniae through the induction of persistent anti-polysaccharide antibodies, and by priming for a rapid secondary antibody response. Memory B cells (BMEM) generated during an initial immune response are responsible for both the more rapid and quantitatively greater secondary antibody response and are also thought to contribute to the ongoing production of plasma cells providing long-term antibody persistence. We recruited 3.5-year-old children who had participated in a previous clinical trial comparing infant immunization with either a 7-valent (PCV-7) or a 13-valent pneumococcal conjugate vaccine (PCV-13) to investigate whether prior priming with pneumococcal antigens influences BMEM responses. Blood was taken before and 1month after a PCV-13 booster. BMEM were quantified using a cultured ELISpot assay for pneumococcal serotypes 1, 3, 4, 14, 19A, 23F, and with diphtheria and tetanus toxoid as controls, and then correlated with serotype-specific IgG concentrations and opsonophagocytic activity (OPA) titers. In total, blood samples from 62 participants were available for analysis. Serotype-specific BMEM frequencies were generally low at baseline (before boost) although for serotypes 14 and 3, they were significantly higher in children primed with PCV-13 than PCV-7 primed children. Following the PCV-13 booster, BMEM frequencies increased and were not different between the groups for all serotypes. A strong inverse correlation was found between antibody concentrations and OPA titers at baseline and BMEM following booster vaccination for serotype 3 but not for other serotypes suggesting that, for this serotype, pre-existing serotype-specific antibodies may inhibit BMEM formation in response to vaccination. Clinicaltrials.gov registration number: NCT01095471.