Plasma and memory B-cell kinetics in infants following a primary schedule of CRM 197-conjugated serogroup C meningococcal polysaccharide vaccine

Abstract

The induction of persistent protective levels of pathogen-specific antibody is an important goal of immunization against childhood infections. However, antibody persistence is poor after immunization in infancy versus later in life. Serogroup C meningococci (MenC) are an important cause of bacteraemia and meningitis in children. The use of protein-polysaccharide conjugate vaccines against MenC has been associated with a significant decline in the incidence of invasive disease. However, vaccine effectiveness is negligible by more than 1 year after a three-dose priming series in infancy and corresponds to a rapid decline in antibody following an initial immune response. The cellular mechanisms underlying the generation of persistent antibody in this age group are unclear. An essential prelude to larger studies of peripheral blood B cells is an understanding of B-cell kinetics following immunization. We measured MenC- and diphtheria-specific plasma and memory B-cell kinetics in infants receiving a CRM(197) (cross-reactive material; mutant diphtheria toxoid)-conjugated MenC vaccine at 2, 3 and 4 months of age. Plasma cell responses were more delayed after the first dose when compared with the rapid appearance of plasma cells after the third dose. Memory B cells were detectable at all time-points following the third dose as opposed to the low frequency seen following a first dose. This study provides data on B-cell kinetics following a primary schedule of immunization in young infants upon which to base further studies of the underlying cellular mechanism of humoral immunity.

Figure 1

Serogroup C meningococcal (MenC) polysaccharide-specific plasma cell frequencies after the first dose (2 months of age) and MenC polysaccharide- and diphtheria-specific plasma cell frequencies after the third dose (4 months of age) of MenC polysaccharide/CRM₁₉₇ (cross-reactive material; mutant diphtheria toxoid)-conjugated vaccine given as part of a 2-, 3- and 4-month schedule of infant immunization. MenC polysaccharide-specific plasma cell frequencies are shown in (a) for the 2-month dose and (b) for the 4-month dose. Diphtheria-specific plasma cell frequencies are shown in (c) for the 4-month dose. Each point represents one individual and lymphocytes from different individuals were used for each time-point. The bars indicate median values. ASCs, antibody-secreting cells; PBMCs, peripheral blood mononuclear cells.

Figure 2

Serogroup C meningococcal (MenC) polysaccharide-specific memory B-cell responses after the first dose (2 months of age) and MenC polysaccharide- and diphtheria-specific memory B-cell frequencies after the third dose (4 months of age) of MenC polysaccharide/CRM₁₉₇ (cross-reactive material; mutant diphtheria toxoid)-conjugated vaccine given as part of a 2-, 3- and 4-month schedule of infant immunization. MenC polysaccharide-specific memory B-cell responses are shown in (a) for the 2-month dose and (b) for the 4-month dose. Diphtheria-specfic plasma cell frequencies are shown in (c) for the 4-month dose. Each point represents one individual and lymphocytes from different individuals were used for each time-point. The bars indicate median values. ASCs, antibody-secreting cells; PBMCs, peripheral blood mononuclear cells.

Figure 3

Scatterplot of the frequency of serogroup C meningococcal (MenC) polysaccharide-specific antibody-secreting cells (ASCs) per 2 × 10⁵ lymphocytes from culture at 5 months of age against MenCPS specific antibody concentration (μg/ml) at 5 months of age (Spearman's rho = 0·58, P < 0·01). IgG, immunoglobulin G.