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

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Dengue virus serotype 1 (DENV1) infection poses a significant global health challenge.
• Understanding longitudinal antibody responses is crucial for effective diagnostics and vaccines.
• Controlled human infection models offer a unique platform to study primary DENV1 infection dynamics.

Purpose of the Study:

• To characterize epitope-level antibody responses following primary DENV1 infection.
• To identify specific antigenic regions involved in the humoral immune response.
• To guide the development of improved dengue serodiagnostics.

Main Methods:

• Utilized samples from a controlled human infection model with DENV1 strain 45AZ5.
• Employed peptide microarrays to assess IgM and IgG reactivity against 7,888 overlapping peptides.
• Validated top antigenic candidates using multiplex peptide immunoassays.

Main Results:

• Primary DENV1 infection induced antibody responses targeting both structural and non-structural viral proteins.
• Identified several known and novel antigenic regions with elevated reactivity.
• Highlighted a highly reactive NS1 wing domain epitope with distinct IgM and IgG profiles across infection phases.

Conclusions:

• Detailed insights into humoral immunity following primary DENV1 infection were obtained.
• Specific linear B cell epitopes and antigenic regions were identified.
• These findings can inform the development of novel diagnostic tests for dengue.