The role of immune boosting and waning in shaping dengue epidemic dynamics.

Abstract

Abstract Infection with one of the four dengue viruses (DENV1-4) induces both virus-specific and broadly reactive antibodies that may either provide protection or increase the severity of disease during secondary infection. Re-exposure in those with multiple prior DENV infections may boost immunity and reduce dengue risk and transmission; however, longitudinal studies investigating re-exposure and protective immunity for dengue epidemic dynamics are still lacking. For instance, does the interaction between long-term waning of immunity between infections and re-exposure to DENV or Zika virus (ZIKV) contribute to the epidemic periodicity? Since measuring re-exposure in highly immune individuals is difficult, previous studies have explored the role of boosting in protection against dengue disease but not using longitudinal measures of herd immunity. Here, we utilize both a longitudinal dataset of antibody titers to DENV and ZIKV measured annually in a Nicaraguan cohort from 2004–2021 and a mathematical model incorporating individual antibody boosting, antibody-dependent enhancement and waning to study the role of boosting on dengue transmission dynamics. Our results support our hypothesis that boosts in highly immune individuals contribute to herd immunity, delaying their contribution into the susceptibles and lowering the rate of dengue cases in future epidemics. However, as their immunity wanes due to lower transmission intensity, the susceptible fraction builds up until a major epidemic that includes re-infection of those with high titers. Our study highlights the interaction of immune boosting and waning in highly exposed adults in shaping dengue epidemics and inform vaccine efforts to maintain immunity over the life-course. Supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health & by grants from NIH (P01AI106695)