With evidence of residual vaccine-serotype carriage and disease in settings similar to Malawi, strategies to achieve sustained vaccine-induced antibody titres are required. This is particularly relevant given that most sub-Saharan African countries implementing PCVs have used the same schedule of 3 primary doses with a limited catch-up campaign. In the context of a 3 + 0 PCV13 schedule in a low-income country, we report the absence of a sustained vaccine-induced antibody response to multiple vaccine serotypes beyond the first year of life, potentially resulting in a window of vulnerability to carriage and disease. Our hypothesis that this post-nadir increase is due to accumulating natural exposure is supported by evidence of carriage of all 13 vaccine serotypes and seroincident events for carried serotypes. Antibody profiles were largely consistent across PCV13 vaccine serotypes except for serotype 3, with a vaccine-induced increase peaking at about age 5 months, subsequently falling to a nadir at about age 14 months, before increasing again. Indeed, IgG titres of several vaccine serotypes remained below putative CoPs against carriage and IPD for extended periods: titres of nine vaccine serotypes fell below the aggregate CoP against IPD (0♳5 μg/mL) for a range of 0♲–51♹ months and below serotype-specific CoPs against carriage for all ten vaccine-serotypes evaluated (range 17♶–54♰ months). In this under-5 population in Malawi, with a 3 + 0 PCV13 schedule and a catch-up campaign among children younger than 1 year, vaccine-induced antibody titres against multiple vaccine serotypes were not sustained at a population level beyond the first year of life. We developed a novel linear spline regression model to define population-level serotype-specific immunogenicity profiles. The Lancet Regional Health – Western Pacific.The Lancet Regional Health – Southeast Asia.The Lancet Gastroenterology & Hepatology.
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