Investigating antibody cross-reactivity and transmission dynamics of alphaviruses and flaviviruses using a multiplex serological assay

Yman V.; Rosado J.; Ochida N.; Garcia L.; Gasasira M.-F.; Baudemont G.; Cramer E.; Dupont-Rouzeyrol M.; Huet K.; Douine M.; Sanna A.; Lambert Y.; Carrasco-Escobar G.; Nolasco O.; Gamboa D.; Fall G.; Ndiaye O.; Faye O.; Loucoubar C.; Toure-Balde A.; Niang M.; Vigan-Womas I.; Cauchemez S.; White M.T. · Nature Communications (2026) · DOI: 10.1038/s41467-026-71451-7

Resumen

Accurate serological tools are essential for monitoring the transmission of arboviruses with pandemic potential, yet cross-reactivity between closely related viruses hampers diagnostics and surveillance. Here, we develop a high-throughput multiplex serological assay to quantify antibody responses to 28 antigens from nine arboviruses (dengue, Zika, yellow fever, West Nile, Usutu, Japanese encephalitis, chikungunya (CHIKV), Mayaro (MAYV), and O’nyong-nyong virus) and apply it to over 4000 samples from epidemiologically distinct sites on four continents. We implement a flexible analytical method based on Bayesian finite mixture models and Receiver Operating Characteristic analysis to evaluate assay performance and define seropositivity thresholds. As a case study, we resolve cross-reactive and virus-specific responses for CHIKV and the emerging MAYV by combining competitive immunoassays with mathematical modelling of multiplex serological and epidemiological data. This approach yields cross-reactivity-adjusted estimates of local transmission dynamics, in agreement with existing epidemiological evidence, and reveals that CHIKV is more prone to induce cross-reactive antibody responses than MAYV. Our results demonstrate the power of combining multiplex serology with experimental validation and modelling to disentangle exposure histories in the face of serological cross-reactivity. This integrative approach holds promise for improving arbovirus surveillance, particularly in settings with overlapping transmission of multiple viruses and limited diagnostic capacity. © The Author(s) 2026.

Instituciones: Universidad Peruana Cayetano Heredia