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

Abstract

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. 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, 19A 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. The majority (88%) of the breakthrough infection occurred in children under 7 years old. Infection by serotypes 3 and 19A increased in children aged 5-17 years in 2018-2019. The pre-booster serotype 3- and 19A-specific IgG in both children with breakthrough infection and controls were lower than the IPD protective thresholds (2.83µg/mL for 3; 1.00µg/mL for 19A). 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. 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.