Immune responses and severe dengue: what have we learned?

Area of Science:

• Virology
• Immunology
• Epidemiology

Background:

• Dengue virus (DENV) infections are a growing global health concern.
• Severe dengue poses a significant threat, necessitating improved vaccines and therapeutics.

Purpose of the Study:

• To review recent advancements in understanding immune mechanisms of severe dengue.
• To identify potential therapeutic targets, prognostic markers, and vaccine strategies based on past learnings.

Main Methods:

• Review of current scientific literature on dengue pathogenesis.
• Analysis of viral and host factors contributing to severe dengue.
• Evaluation of immune correlates of protection and disease severity.

Main Results:

• Viraemia extent and duration correlate with disease severity, though variability exists.
• Differences in viraemia, nonstructural protein 1 (NS1) antigenemia, and pathogenicity among DENV serotypes/genotypes are noted.
• Neutralizing antibody levels, specificity, breadth, and functionality are critical for protection.

Conclusions:

• Despite progress, key aspects of dengue pathogenesis, viral/host factors in severe dengue, vascular leak, and immune correlates of protection remain incompletely understood.