Connecting serological data and antigenic maps of dengue viruses to protection and disease severity

SPEAKER: Leah Katzelnick

Postdoctoral Fellow
University of California, Berkeley

ABSTRACT

Dengue viruses 1‐4 (DENV1‐4) are mosquito‐borne flaviviruses that cause ~500,000 severe dengue cases annually. This seminar will present research on the relationships between anti‐DENV neutralizing and binding antibodies and protection against and enhancement of dengue disease. We studied the antigenic relationships among diverse DENV strains using neutralizing antibody titers and found that DENV strains loosely clustered by DENV type, but many strains were equidistant to strains of a heterologous DENV type as to some homologous‐type strains. Further, many primary infection antisera exhibited persistent heterotypic neutralizing antibody titers for years after primary infection. Through examining anti‐DENV antibody responses in a longitudinal pediatric dengue cohort in Managua, Nicaragua, we found that higher pre‐existing anti‐DENV neutralizing and binding antibody titers were associated protection against symptomatic dengue but that pre‐existing anti‐DENV binding antibodies within a narrow range were associated with enhancement of severe dengue disease. Collectively, these findings suggest that DENV strains are not antigenically homogeneous within DENV type, and that primary infection antibody responses are varied and at high levels protect against a heterotypic DENV infection but at intermediate levels can enhance dengue disease.

Streaming video: the seminar will be broadcast live once the event has started. The video recording may also be viewed at a later date. [link]