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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.

Original publication

DOI

10.1016/j.vaccine.2017.03.079

Type

Journal article

Journal

Vaccine

Publication Date

09/05/2017

Volume

35

Pages

2701 - 2708

Keywords

Antibodies, B cells, Children, Conjugate vaccine, Memory, Memory B cells, Persistence, Serotype 3, Streptococcus pneumoniae, Vaccination, Antibodies, Bacterial, B-Lymphocytes, Child, Preschool, Enzyme-Linked Immunospot Assay, Female, Heptavalent Pneumococcal Conjugate Vaccine, Humans, Immunization, Secondary, Immunoglobulin G, Immunologic Memory, Male, Opsonin Proteins, Phagocytosis, Pneumococcal Vaccines, Streptococcus pneumoniae