Clinical features and immune memory of breakthrough infection in children after age-appropriate 13-valent pneumococcal conjugate vaccination in Taiwan

Purpose: As certain vaccine serotypes are still circulating within the community during the PCV13 era, we aimed to delineate the clinical features and assess the immunity following breakthrough infections in children.

Methods: 101 PCVs-vaccinated children < 18 years with culture confirmed PCV13 serotype breakthrough infection (25/101, invasive pneumococcal disease [IPD]) was identified in Taiwan in 2015-2019. Immunoglobulin G (IgG) antibody levels, IgM⁺ memory B cells (MBCs), and isotype-switched immunoglobulin (sIg⁺) MBC specific to serotypes 3, 14, 19 A were assessed prior to and one month after an additional PCV13 booster in 9 patients. A cohort of 89 previously vaccinated, healthy children were enrolled as controls.

Results: The majority (88%) of the breakthrough infection occurred in children under 7 years old. Infection by serotypes 3 and 19 A increased in children aged 5-17 years in 2018-2019. The pre-booster serotype 3- and 19 A-specific IgG in both children with breakthrough infection and controls were lower than the IPD protective thresholds (2.83 µg/mL for 3; 1.00 µg/mL for 19 A). Breakthrough infected children showed higher geometric mean ratio in serotype-specific IgG, IgM⁺ MBCs and sIg⁺ MBC after an additional PCV13 booster, compared to the controls.

Conclusions: Most breakthrough infections occurred in previously healthy preschool-aged children, but such infections may still occur in school-aged children due to waning immunity. Breakthrough infections may also enhance the anamnestic response elicited by PCV13.