Zika Virus Infection Increases Risk of Subsequent Severe Dengue Disease

Flaviviruses cause enormous global morbidity and mortality, making vaccine development a public health priority. The four serotypes of dengue virus (DENV) are primary targets of these efforts. Though one licensed DENV vaccine (Dengvaxia) is currently available, its impact is mitigated by the increased incidence of severe dengue disease in vaccinated patients who were previously DENV-naïve. This is due to antibody-dependent enhancement (ADE), where cross-reactive, non-neutralizing antibodies to one serotype promote infection by a different serotype. Given Zika virus’s (ZIKV) structural and geographical similarities to DENV, a major concern is whether these ADE-related immune interactions are relevant to vaccine generation against ZIKV. In their new study in Science, Katzelnick et al. studied prospective cohorts in Nicaraguan pediatric populations exposed to sequential DENV1-3 (2004-2015), ZIKV (2016-2017), and DENV2 (2018-2020) epidemics. They found that the risk of severe DENV2 disease was increased by either prior DENV or ZIKV infection, as well as by prior DENV and subsequent ZIKV infections. The risk was decreased with multiple previous DENV infections. Intermediate titers of ZIKV or DENV antibodies in these patients were linked to more serious disease caused by later DENV2 or DENV3 infections, but not by DENV1 or ZIKV. In contrast, more elevated anti-DENV titers were protective against DENV1, DENV3, or ZIKV symptomatic disease, but were not against DENV2. This important study spotlights the complex intricacies of the host immune response to prior DENV and/or ZIKV infection, where the magnitude of clinical disease with secondary infection varies with virus type or serotype, antibody titer, and sequence of infection. These findings underscore the challenges inherent in the process to create safe and effective DENV and ZIKV vaccines.

With the ongoing pandemic, it is perhaps understandable that the persistent worldwide threat of other RNA virus pathogens, including flaviviruses, has been superseded by that of SARS-CoV-2. Nevertheless, flavivirus research must continue, and GeneTex is proud to offer the most comprehensive, well-validated, and widely published research antibody portfolios against DENV, ZIKV, and other flaviviruses.

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