Abstract
BackgroundPlain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM).MethodsNeonatal mice were primed subcutanously (s.c.) or intranasally (i.n.) with pneumococcal conjugate (Pnc1-TT) and the adjuvant LT-K63, and boosted with PPS+LT-K63 or saline 1, 2 or 3 times with 16 day intervals. Seven days after each booster, spleens were removed, germinal centers (GC), IgM+, IgG+ follicles and PPS-specific antibody secreting cells (AbSC) in spleen and BM enumerated.ResultsPPS booster s.c., but not i.n., compromised the Pnc1-TT-induced PPS-specific Abs by abrogating the Pnc1-TT-induced GC reaction and depleting PPS-specific AbSCs in spleen and limiting their homing to the BM. There was no difference in the frequency of PPS-specific AbSCs in spleen and BM between mice that received 1, 2 or 3 PPS boosters s.c.. Repeated PPS+LT-K63 booster i.n. reduced the frequency of PPS-specific IgG+ AbSCs in BM.ConclusionsPPS booster-induced hyporesponsiveness is caused by abrogation of conjugate-induced GC reaction and depletion of PPS-specific IgG+ AbSCs resulting in no homing of new PPS-specific long-lived plasma cells to the BM or survival. These results should be taken into account in design of vaccination schedules where polysaccharides are being considered.
Highlights
High susceptibility to infectious diseases by polysaccharide (PS) encapsulated bacteria like Streptococcus pneumoniae characterizes the neonatal and infant period mainly due to the inability of the neonates and infants to elicit immune response to the PS capsule, a T cell independent type 2 (TI-2) antigen [1,2]
The results show that a single dose of plain pneumococcal polysaccharide (PPS)-1 s.c. is sufficient to completely deplete the PPS of serotype 1 (PPS-1)-specific memory cell and antibody secreting cells (AbSC) pool established by pneumococcal conjugate priming in neonatal mice, since PPS-1 abrogates the conjugate-induced germinal center reaction, causing hyporesponsiveness
No difference was observed in the frequency of PPS-1-specific IgG+ AbSCs in the bone marrow (BM) of mice that received PPS-1 booster compared with saline, but there was a difference compared with Pnc1-TT booster (Figure 1)
Summary
High susceptibility to infectious diseases by polysaccharide (PS) encapsulated bacteria like Streptococcus pneumoniae characterizes the neonatal and infant period mainly due to the inability of the neonates and infants to elicit immune response to the PS capsule, a T cell independent type 2 (TI-2) antigen [1,2]. Neonates become colonized by pneumococci soon after birth, in particular in developing countries, where prevalence of pneumococcal carriage is high [3]. Colonization and prolonged carriage are believed to contribute to the high incidence and early onset of pneumococcal diseases in developing countries [4]. Hyporesponsiveness, defined as a lower antibody (Ab) level after the second immunization than after the first, has been observed after repeated immunizations with plain pneumococcal PS vaccines (PPV) in infants and toddlers for many of the serotypes [6,7], as well as in the elderly [8]. Pneumococcal conjugate vaccines (PCV), unlike PPV, elicit IgG Abs and immunological memory during infancy [10]. Plain pneumococcal polysaccharide (PPS) booster administered during second year of life has been shown to cause hyporesponsiveness. We assessed the effects of PPS booster on splenic memory B cell responses and persistence of PPS-specific long-lived plasma cells in the bone marrow (BM)
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