Pneumococcal Conjugate Vaccine Schedules Shape Serotype-Specific Memory B-Cell Responses

Reduced-dose pneumococcal conjugate vaccine (PCV) schedules (1+1; one primary and one booster) are now endorsed by the World Health Organisation under specific circumstances. Serotype-specific memory B cells (BMEM) are a marker of long-term protection but data from infant reduced-dose trials remain limited. As part of a randomised controlled trial in Vietnamese infants, we characterised serotype-specific BMEM responses in randomised subsets (N=50 per vaccine group per timepoint) following 0+1 (at 12 months of age) or 1+1 (2 and 12 months of age) schedules of PCV10 or PCV13, using a multimer spectral flow cytometry approach. Blood samples were collected at 12 months of age (baseline) and at day 7 and day 28 post-vaccination. A one or two dose schedule of either PCV induced robust serotype-specific BMEM responses at day 7 and day 28 for most serotypes. PCV13 generated earlier and higher BMEM responses than PCV10, while 1+1 schedules for either PCV produced higher BMEM responses than the 0+1 schedules at day 7. By day 28, these differences between the 0+1 and 1+1 schedules were no longer apparent. Notably, BMEM responses for serotypes 6B and 23F were detectable even in infants who did not achieve protective levels of serotype-specific IgG greater or equal to 0.35 ug/mL. PCV13 generated higher plasmablast and plasma cell responses by day 7, and higher cTfh responses by day 28, compared to PCV10. These findings show that 1+1 schedules of PCV10 or PCV13 induce robust BMEM responses, with important implications for the evaluation of PCVs and understanding long-term protection.