ORCID

0000-0002-3454-7325

Keywords

Antibody, Dengue, Zika, ADE, Mexico

Subject Categories

Infectious Disease

Abstract

The Aedes mosquito-borne flaviviruses Zika (ZIKV) and dengue (DENV-1-4) cause an estimated 400 million annual infections globally and pose an increasing threat to public health. Typically, individuals infected with ZIKV or a DENV serotype generate neutralizing serotype-specific antibodies and non-neutralizing, cross-reactive antibodies that bind multiple flaviviruses. Upon secondary heterotypic infection, pre-existing antibodies can either protect or exacerbate disease through antibody dependent enhancement (ADE). ADE occurs when non- or sub-neutralizing concentrations of cross-reactive antibodies facilitate viral uptake into FcγR-bearing myeloid cells, enabling infection of otherwise non-permissive cells and driving severe disease. To date, ADE has not been characterized at a population level across all five flaviviruses, and the relationship between neutralizing and enhancing antibodies within the same individuals remains poorly understood. We optimized a K562 cell-based in vitro assay to generate ADE profiles for ZIKV and DENV-1-4 and applied it to 25 participant sera collected from the 2022 YABC pediatric cohort in Mérida, Mexico, a flavivirus-endemic region. Sera were selected for high ZIKV-neutralizing activity with one seronegative reference. We extracted three ADE parameters per participant: serum dilution at maximum enhancement (higher values mean more dilution required for ADE), area under the curve (magnitude and breadth of enhancement), and maximum infection (highest infection reached). ADE profiles varied among individuals and across viruses within the same individual. ZIKV enhancement peaked at greater serum dilutions than DENV-1,3,4, indicating ZIKV-binding antibodies were present above the enhancing window, leaving individuals unlikely to be at ZIKV-ADE risk in 2022. DENV-2 generated peak infection, suggesting high DENV-2-ADE risk in 2022. ZIKV ADE also correlated strongly with ZIKV neutralizing antibody titers – higher ZIKV neutralizing titers were associated with greater ADE once serum was diluted into sub-neutralizing range. Characterizing how protective and enhancing antibody responses interact within flavivirus-endemic populations can inform disease interventions and vaccine strategies.

Completion Date

2026

Semester

Summer

Committee Chair

Earnest, James

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Document Type

Thesis

Language

English

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