Maternally derived antibody titer dynamics and risk of hospitalized infant dengue disease

Maternally derived antibody titer dynamics and risk of hospitalized infant dengue disease

Infants less than 1 y of age experience high rates of dengue disease in dengue virus (DENV) endemic countries. This burden is commonly attributed to antibody-dependent enhancement (ADE), whereby concentrations of maternally derived DENV antibodies become subneutralizing, and infection-enhancing. Und...

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Published in:Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 41; p. e2308221120
Main Authors: O'Driscoll, Megan, Buddhari, Darunee, Huang, Angkana T, Waickman, Adam, Kaewhirun, Surachai, Iamsirithaworn, Sopon, Khampaen, Direk, Farmer, Aaron, Fernandez, Stefan, Rodriguez-Barraquer, Isabel, Srikiatkhachorn, Anon, Thomas, Stephen, Endy, Timothy, Rothman, Alan L, Anderson, Kathryn, Cummings, Derek A T, Salje, Henrik
Format: Journal Article
Language:English
Published: United States National Academy of Sciences 10-10-2023
Subjects:
Age composition
Antibodies
Antibodies, Neutralizing
Antibodies, Viral
Antibody-Dependent Enhancement
Babies
Biological Sciences
Birth rate
Dengue
Dengue fever
Dengue hemorrhagic fever
Dengue Virus
Epidemiology
Health risks
Hospitalization
Humans
Infant
Infant, Newborn
Infants
Mathematical models
Neonates
Risk
Severe Dengue
Vector-borne diseases
Thailand
antibody dependent enhancement
maternal antibodies
dengue
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Summary:Infants less than 1 y of age experience high rates of dengue disease in dengue virus (DENV) endemic countries. This burden is commonly attributed to antibody-dependent enhancement (ADE), whereby concentrations of maternally derived DENV antibodies become subneutralizing, and infection-enhancing. Understanding antibody-related mechanisms of enhanced infant dengue disease risk represents a significant challenge due to the dynamic nature of antibodies and their imperfect measurement processes. Further, key uncertainties exist regarding the impact of long-term shifts in birth rates, population-level infection risks, and maternal ages on the DENV immune landscape of newborns and their subsequent risks of severe dengue disease in infancy. Here, we analyze DENV antibody data from two infant cohorts (N = 142 infants with 605 blood draws) and 40 y of infant dengue hospitalization data from Thailand. We use mathematical models to reconstruct maternally derived antibody dynamics, accounting for discretized measurement processes and limits of assay detection. We then explore possible antibody-related mechanisms of enhanced infant dengue disease risk and their ability to reconstruct the observed age distribution of hospitalized infant dengue cases. We find that ADE mechanisms are best able to reconstruct the observed data. Finally, we describe how the shifting epidemiology of dengue in Thailand, combined with declining birth rates, have decreased the absolute risk of infant dengue disease by 88% over a 40-y period while having minimal impact on the mean age of infant hospitalized dengue disease.
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Edited by Pejman Rohani, The University of Georgia, Athens, GA; received May 19, 2023; accepted August 12, 2023 by Editorial Board Member Bruce R. Levin
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2308221120