What question did this study set out to answer?

This research aims to determine how previous dengue infections shape antibody responses during secondary infection.

July 30, 2026

Infection history shapes envelope-specific IgG repertoires with convergent neutralization from multiple lineages in secondary dengue 2259474

DTDouglas TownsendThe University of Texas at Austin TSTulika SinghMarymount University CMChristina MartinsThe University of Texas at Austin

Key Points

This research aims to determine how previous dengue infections shape antibody responses during secondary infection.
High-resolution proteomic analysis of circulating IgG specific to dengue envelope dimer.
Study involved pediatric participants with a history of DENV2 and DENV3 infections.
Recombinant monoclonal antibodies were created for further epitope mapping and neutralization testing.
Over 87% of envelope-specific IgG lineages were cross-reactive.
67% of these lineages neutralized at least two serotypes with NT50 values ranging from 0.19 to 1.4 µg/mL.
Distinct epitope profiles were found despite similar neutralizing activities in donors with different secondary infections.

Abstract

Abstract Introduction Dengue virus (DENV1-4) infects an estimated 400 million people annually. Severe disease is often linked to antibody-dependent enhancement (ADE) during secondary infection, whereby cross-reactive, non-neutralizing antibodies facilitate viral entry. While primary infection elicits protective serotype-specific and enhancing cross-reactive antibodies, secondary infection is thought to elicit broadly neutralizing antibodies that confer heterotypic protection. However, it remains unknown whether post-secondary plasma neutralization is driven by a few dominant clonotypes or distributed across diverse broadly neutralizing lineages. Methods We applied high-resolution proteomic analysis of DENV envelope (E) dimer-specific circulating immunoglobulin (IgG) at post-secondary late convalescence (4-6 months post-illness) to quantitatively profile the plasma antibody repertoire with monoclonal resolution in participants of a pediatric hospital-based study in Nicaraguan (N = 3 DENV2, N = 4 DENV3). Recombinant monoclonal antibodies (mAbs) were constructed from the most abundant serological lineages for epitope mapping and neutralization assays. Results Across five donors, 87% of E-specific IgG lineages were cross-reactive and 67% neutralized at least two serotypes. Of these, 64% cross-neutralized DENV1-4 with geometric mean NT50 values between 0.19 — 1.4 µg/mL. Analysis of abundant IgG lineages from two donors, either secondary DENV2 or DENV3 infection, revealed distinct epitope profiles on the E dimer despite similar cross-neutralizing activity. Conclusion Our findings demonstrate functional convergence to DENV cross-neutralization despite divergent epitope profiles in donors with different secondary DENV infection histories. Together, this suggests that DENV cross-neutralizing antibodies are abundant in post-secondary plasma, and that there are several mechanisms and lineages that enable broad neutralization of DENV1-4. Funding Source National Institute of Health R21AI176011 and National Institute of Allergy and Infectious Disease P01AI106695 Topic Categories Viral Immunology (VIR)

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