Dengue antibody dynamics resolved at epitope level using a dengue 1 human infection model

To characterize longitudinal antibody responses at the epitope level following primary dengue virus serotype 1 (DENV1) infection in a controlled human infection model, and to identify antigenic regions that could guide the development of improved dengue serodiagnostics.

In this study, we leveraged samples from a dengue human infection model, in which nine flavivirus-naïve individuals were experimentally infected with the under-attenuated DENV1 strain 45AZ5. IgM and IgG reactivity to 7888 overlapping 15-mer peptides spanning the dengue, Zika, yellow fever, and chikungunya virus proteomes was evaluated using peptide microarrays. Top candidates were validated using multiplex peptide immunoassays.

Primary DENV1 infection elicited responses primarily targeting the DENV proteome, including antigenic regions in both structural and non-structural proteins. Several known and novel antigenic regions showed elevated reactivity upon primary infection, notably the highly reactive NS1 wing domain epitope with distinct IgM and IgG profiles in early and late convalescent phases.

These findings provide detailed insight into humoral responses following primary DENV1 infection and highlight specific linear B cell epitopes and antigenic regions that could inform the development of improved diagnostic tests based on defined linear B cell epitopes.