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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月15日

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  • Victor Yman,
  • Jason Rosado,
  • Noé Ochida,
  • Laura Garcia,
  • Marie-Fabrice Gasasira,
  • Gaëlle Baudemont,
  • Estee Cramer,
  • Myrielle Dupont-Rouzeyrol,
  • Karl Huet,
  • Maylis Douine,
  • Alice Sanna,
  • Yann Lambert,
  • Gabriel Carrasco-Escobar,
  • Oscar Nolasco,
  • Dionicia Gamboa,
  • Gamou Fall,
  • Oumar Ndiaye,
  • Oumar Faye,
  • Cheikh Loucoubar,
  • Aissatou Toure-Balde,
  • Makhtar Niang,
  • Ines Vigan-Womas,
  • Simon Cauchemez,
  • Michael T. White

摘要

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.