A Multiplex Serological Assay for Quantification of Arbovirus Antibody Kinetics and Neutralizing Antibodies
Garcia, L.; Yman, V.; Gasasira, M.-F.; Donnadieu, F.; Cappuccio, L.; Hoinard, D.; Despres, P.; Manuguerra, J.-C.; Yoon, I.-K.; Hunsawong, T.; Alera, M. T. P.; Gurley, E. S.; Vasilakis, N.; Weaver, S. C.; Rahman, Z.; Dorigatti, I.; Drakeley, C.; Vigan-Womas, I.; Niang, M.; Salje, H.; Vanhomwegen, J.; White, M.
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Arboviruses such as dengue virus (DENV) and chikungunya virus (CHIKV) pose major global health threats. To support serological surveillance and study cross-reactivity, an in-house multiplex bead-based immunoassay was developed to measure IgG responses against a wide panel of orthoflavivirus and alphavirus antigens. Samples from Senegal, France, the Philippines, and Bangladesh enabled analyses to be carried out in endemic and non-endemic regions. IgG kinetics following DENV1 and CHIKV infections revealed virus-specific temporal profiles and identified antigens, such as CHIKV E2 and VLP, as well as DENV1 EDIII and SNAP-tagged EDIII, as promising markers for serosurveillance. A two-step Random Forest model was used to classify PRNT-positive samples and predict PRNT titers. CHIKV showed a strong correlation between IgG and PRNT titers (R2 = 0.71), while DENV1 showed weaker performance (R2 = 0.42). These results support the use of multiplex serology for arbovirus surveillance and highlight the limitations of using binding antibodies to predict neutralisation, particularly for orthoflaviviruses.
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