Zika virus infection enhances future risk of severe dengue disease

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Science  28 Aug 2020:
Vol. 369, Issue 6507, pp. 1123-1128
DOI: 10.1126/science.abb6143

Double whammy

Dengue and Zika virus epidemics have been lapping each other around the globe. These are closely related mosquito-borne viruses with about 40% homology within the envelope protein. We know that subsequent dengue infections bring a risk of antibody-dependent disease enhancement. Whereas emphasis has been placed on how prior dengue immunity affects Zika infection, little is known about how prior Zika immunity may affect dengue disease. Katzelnick et al. have been following a well-characterized and established pediatric cohort in Nicaragua who were serially exposed to both flaviviruses in recent years (see the Perspective by Clapham). This study shows not only that a previous history of just one round of dengue is a problem but also that prior Zika immunity creates an increased risk for severe dengue virus sereotype 2 infection. By contrast, multiple infections raise antibodies to protective levels.

Science, this issue p. 1123; see also p. 1055


The Zika pandemic sparked intense interest in whether immune interactions among dengue virus serotypes 1 to 4 (DENV1 to -4) extend to the closely related Zika virus (ZIKV). We investigated prospective pediatric cohorts in Nicaragua that experienced sequential DENV1 to -3 (2004 to 2015), Zika (2016 to 2017), and DENV2 (2018 to 2020) epidemics. Risk of symptomatic DENV2 infection and severe disease was elevated by one prior ZIKV infection, one prior DENV infection, or one prior DENV infection followed by one ZIKV infection, compared with being flavivirus-naïve. By contrast, multiple prior DENV infections reduced dengue risk. Further, although high preexisting anti-DENV antibody titers protected against DENV1, DENV3, and ZIKV disease, intermediate titers induced by previous ZIKV or DENV infection enhanced future risk of DENV2 disease and severity, as well as DENV3 severity. The observation that prior ZIKV infection can modulate dengue disease severity like a DENV serotype poses challenges to development of dengue and Zika vaccines.

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