Dengue virus controlled human challenge reveals that preexisting immunity shapes viral replication and broadly protective responses.

In a phase 1 challenge trial of 45 healthy adults, secondary heterotypic dengue infection increased viremia and immunogenicity, while baseline antibodies linked to either controlled replication or dysregulated inflammation.

• Why it matters: Immune history and early responses in dengue are not confirmed due to limits of animal models and the timing of clinical presentation after peak viremia.
• What they did: The study compared primary, secondary, and tertiary infection using a heterotypic full-length attenuated dengue virus challenge, measuring viremia, neutralizing antibodies, T cell responses, and baseline antibody effects in vitro.
• The result: Baseline antibodies that most efficiently increased replication predicted delayed immune activation, highest viremia, strong acute responses, and waning of potent CD8+ T cells and antibodies; higher baseline NS1 antibodies predicted early interferon, viremia control, and enduring potent B and T cells.