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Waning of PCV13 vaccine-induced antibody levels within the first year of life, using a 3+0 schedule: an observational population-level serosurveillance study among children under 5 years old in Blantyre, Malawi

Article scientifique 2022 Anglais

Résumé

ABSTRACT Background Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibody, effectively reducing vaccine-serotype (VT) carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty around correlate of protection (CoP) estimates and with persistent VT carriage and VT-IPD following PCV13 introduction, we undertook population-level immunogenicity profiling among children <5 years in Blantyre, Malawi. Methods For 638 children, capsule-specific IgG to PCV13 VTs, two non-VTs, and IgG to three pneumococcal proteins were measured using an enzyme-linked immunosorbent assay and a direct-binding electrochemiluminescence-based multiplex assay. A linear spline regression model estimated population-level, serotype-specific immunogenicity profiles. A linear regression model was used to validate putative CoPs. Findings Immunogenicity profiles revealed a consistent pattern among VTs except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3 there was no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination-nadir (11·2 [19F, 23F] to 27·3 [7F] months). Titres dropped below IPD CoPs among 9 VTs and below carriage CoPs for 10 VTs. Study data estimated a range of carriage CoPs (0·50μg/mL to 2·5μg/mL). Increasing antibody among older children and seroincident events were consistent with ongoing VT exposure. Interpretation A 3+0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several VTs, potentially contributing to persistent VT carriage and residual VT-IPD in Malawi and other similar settings. Funding Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health & Care Research.

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Swarthout, T., Henrion, M., Thindwa, D., Meiring, J., Mbewe, M., Brown, C., Msefula, J., Moyo, B., Mataya, A., Barnaba, S., Pearce, E., Gordon, M., Goldblatt, D., French, N., Heyderman, R. (2022). Waning of PCV13 vaccine-induced antibody levels within the first year of life, using a 3+0 schedule: an observational population-level serosurveillance study among children under 5 years old in Blantyre, Malawi. https://doi.org/10.1101/2022.04.21.22272868

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Auteur(s)

Todd D. Swarthout Marc Henrion Deus Thindwa James Meiring Maurice Mbewe Comfort Brown Jacquline Msefula Brewster Moyo Andrew A. Mataya Susanne Barnaba Emma Pearce Melita A. Gordon David Goldblatt Neil French Robert S. Heyderman

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