Investigating antibody cross-reactivity and transmission dynamics of alphaviruses and flaviviruses using a multiplex serological assay
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.
Authors
- Myrielle Dupont‐Rouzeyrol (ORCID: https://orcid.org/0000-0002-6991-4893)
- Dionicia Gamboa (ORCID: https://orcid.org/0000-0002-1420-7729)
- Maylis Douine (ORCID: https://orcid.org/0000-0003-4616-6690)
- Simon Cauchemez (ORCID: https://orcid.org/0000-0001-9186-4549)
- Noé Ochida (ORCID: https://orcid.org/0000-0003-2347-6426)
- Victor Yman (ORCID: https://orcid.org/0000-0001-7267-0749)
- Michael T. White
- Gamou Fall (ORCID: https://orcid.org/0000-0001-5035-1325)
- Karl Huet (ORCID: https://orcid.org/0009-0003-0707-6606)
- Makhtar Niang (ORCID: https://orcid.org/0000-0003-0810-4595)
- Yann Lambert (ORCID: https://orcid.org/0000-0001-9020-3263)
- Aïssatou Touré-Baldé (ORCID: https://orcid.org/0000-0003-0090-9495)
- Oscar Nolasco (ORCID: https://orcid.org/0000-0002-5672-5516)
- Jason Rosado (ORCID: https://orcid.org/0000-0003-4834-2088)
- Gaëlle Baudemont (ORCID: https://orcid.org/0009-0006-0345-7489)
- EM Cramer
- Marie-Fabrice Gasasira
- Oumar Ndiaye
- Laura Garcia
- Gabriel Carrasco-Escobar
- Ines Vigan-Womas
- Cheikh Loucoubar
- Alice Sanna
- Oumar Faye
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Institut Pasteur (FR)
- Universidad Peruana Cayetano Heredia (PE)
- Université Paris Cité (FR)
- University of French Guiana (GF)
- Karolinska Institutet (SE)
- Sorbonne Paris Cité (FR)
- Stockholm South General Hospital (SE)
- Centre Hospitalier Andrée Rosemon (GF)
- Institut Pasteur de Dakar (SN)
- Institut Pasteur de Nouvelle Calédonie (NC)
- Institut de Recherche pour le Développement (FR)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-04-15
- DOI
- https://doi.org/10.1038/s41467-026-71451-7
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Agence Nationale de la Recherche
- Svenska Sällskapet för Medicinsk Forskning
- Svenska Läkaresällskapet
- National Institutes of Health
- European and Developing Countries Clinical Trials Partnership