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

Driscoll, Megan O.; 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

doi:10.1073/pnas.2308221120

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

Author(s)

Driscoll, Megan O.

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

Date Issued

October 3, 2023

Type

Article

DOI

10.1073/pnas.2308221120

Abstract

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.

Citation

Proceedings of the National Academy of Sciences of the United States of America, 120(41), 2023