Dengue virus antibody database: Systematically linking serotype-specificity with epitope mapping in dengue virus

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Dengue virus (DENV) infections often lead to severe illness, particularly during secondary infections, indicating a role for pre-existing immunity in disease pathogenesis.
• Primary DENV infections elicit serotype-specific antibody responses, whereas secondary infections are characterized by broadly cross-reactive antibodies.

Purpose of the Study:

• To investigate the shift in antibody fine-specificity between primary and secondary DENV infections.
• To understand the link between antibody epitope-specificity and serotype-specificity in dengue pathogenesis.

Main Methods:

• Assembled the Dengue Virus Antibody Database with over 400 DENV-specific monoclonal antibodies (mAbs).
• Annotated mAbs with origin, binding/neutralization data against all four DENV serotypes, and epitope mapping data.
• Generated composite epitope maps of primary and secondary antibody responses using epitope mapping and activity information.

Main Results:

• Identified distinct epitope-specificity patterns between primary and secondary DENV infections.
• Secondary responses preferentially target a specific subset of epitopes, including cross-reactive epitopes like the fusion-loop and E-dimer regions.
• Observed increased cross-reactivity in typically serotype-specific epitope regions during secondary infections.

Conclusions:

• Results support the role of pre-existing cross-reactive memory B cells in shaping secondary antibody responses.
• Secondary responses broaden in cross-reactivity and focus on specific epitopes, some associated with poor neutralization and antibody-dependent enhancement.
• Understanding these epitope-specific responses is crucial for dengue pathogenesis and vaccine development.