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- Title
Antigenic distance between primary and secondary dengue infections correlates with disease risk.
- Authors
Wang, Lin; Huang, Angkana T.; Katzelnick, Leah C.; Lefrancq, Noémie; Escoto, Ana Coello; Duret, Loréna; Chowdhury, Nayeem; Jarman, Richard; Conte, Matthew A.; Berry, Irina Maljkovic; Fernandez, Stefan; Klungthong, Chonticha; Thaisomboonsuk, Butsaya; Suntarattiwong, Piyarat; Vandepitte, Warunee; Whitehead, Stephen S.; Cauchemez, Simon; Cummings, Derek A. T.; Salje, Henrik
- Abstract
Many pathogens continuously change their protein structure in response to immune-driven selection, resulting in weakened protection even in previously exposed individuals. In addition, for some pathogens, such as dengue virus, poorly targeted immunity is associated with increased risk of severe disease through a mechanism known as antibody-dependent enhancement. However, it remains unclear whether the antigenic distances between an individual's first infection and subsequent exposures dictate disease risk, explaining the observed large-scale differences in dengue hospitalizations across years. Here, we develop a framework that combines detailed antigenic and genetic characterization of viruses with details on hospitalized cases from 21 years of dengue surveillance in Bangkok, Thailand, to identify the role of the antigenic profile of circulating viruses in determining disease risk. We found that the risk of hospitalization depended on both the specific order of infecting serotypes and the antigenic distance between an individual's primary and secondary infections, with risk maximized at intermediate antigenic distances. These findings suggest that immune imprinting helps determine dengue disease risk and provide a pathway to monitor the changing risk profile of populations and to quantifying risk profiles of candidate vaccines. Editor's summary: It is established that a secondary dengue virus (DENV) infection can cause severe disease through antibody-dependent enhancement, but much of this work has considered DENV serotypes as a single entity. To provide a more granular look at how between- and within-serotype variability can influence risk of severe dengue, Wang et al. developed a framework combining antigenic and genetic characterization of DENV isolates with dengue case data. The authors found that disease severity correlated with the order of infecting serotypes as well as the antigenic distance between the infecting viruses. Intermediate antigenic distances seemed to result in more severe disease. This framework, coupled with real-world data, could both help predict future outbreaks of severe disease and inform vaccine design. —Courtney Malo
- Publication
Science Translational Medicine, 2024, Vol 16, Issue 744, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.adk3259