Antigenic diversity and dengue disease risk

Area of Science:

• Virology
• Immunology
• Epidemiology

Background:

• Pathogen evolution, particularly antigenic drift, can evade immune responses, leading to reduced vaccine efficacy and increased disease severity.
• Antibody-dependent enhancement (ADE) in dengue virus infections highlights how prior immunity can paradoxically increase the risk of severe disease.
• Understanding the impact of antigenic distance between sequential infections on disease risk is crucial for managing dengue outbreaks.

Approach:

• Developed an inferential framework integrating viral antigenic and genetic data with 21 years of hospitalized case data from Bangkok, Thailand.
• Analyzed the relationship between the antigenic profile of circulating dengue virus serotypes and patient hospitalization risk.
• Investigated the influence of the order of serotype exposure and antigenic distance on disease severity.

Key Points:

• Dengue virus hospitalization risk is determined by the specific sequence of infecting serotypes.
• Intermediate antigenic distances between primary and secondary dengue virus infections correlate with maximized hospitalization risk.
• Immune imprinting, where initial immune responses shape subsequent responses, appears to be a significant factor in dengue disease risk.

Conclusions:

• The antigenic profile of circulating viruses, influenced by immune imprinting, critically determines dengue disease risk.
• This framework enables monitoring of evolving population risk profiles for dengue.
• Quantifying the risk profiles of candidate dengue vaccines can be informed by these findings.