Dengue as the new Vaccinia: newly discovered cross-reactivity of DENV and Zika Virus

The most recent Zika Virus (ZIKV) outbreak in the Americas has motivated extensive research into not only the biochemistry of this peculiar flavivirus, but also into risk factors for ZIKV infection and research to understand the spread of ZIKV. Particularly of note, research from Rodriguez-Barraquer et al. published February 8^th suggests that prior Dengue infection and corresponding immune-reactivity to DENV significantly reduces the risk of ZIKV infection in the epicenter of this 2015 ZIKV outbreak. Despite a 73% attack rate of ZIKV in this community, it was found that individuals who had pre-existing antibodies to DENV had lower risk of both infection and in the case of infection, more mild and manageable symptoms.

Development of an IgG3 test, which was able to distinguish DENV from ZIKV, allowed for researchers to track the long-term development of the ZIKV outbreak within this context. The use of this assay was thoroughly confirmed for specificity and sensitivity, and was able to show subtle trends in the seropositivity of this population for individually Zika and Dengue. In doing so, a trend of those individuals with Dengue seropositivity were shown to have upwards of a 35% reduction in odds of being ZIKV-positive after the outbreak. Additionally, this dependence was approximately linear with respect to DENV antibody concentrations in the body, suggesting that higher reactivity to DENV is correlated with even lower rates of ZIKV infection. This was emphasized further when it was confirmed that ZIKV attack rates were higher in urban regions, where DENV infection is less common than in the studied epicenters (usually lying on the borders of forests/mosquito habitats and smaller towns).

Epidemiologically, this correlation was proposed to be related to the dissipation of ZIKV infection, as the regions where ZIKV was most common were areas also endemic for Dengue infection. Additionally, the nature of Dengue IgG3 antibodies, as detected in the used assays, are known to persist for up to 6 months, suggesting that more recent infection (which would result in higher titers of antibody) was more closely related to a lack of ZIKV infection. These conclusions warrant further research as they suggest that an effective DENV vaccine would also be preventative for ZIKV infection. However, this is a major challenge for researchers as the strains of DENV known to infect humans are known to cause much worse symptoms of Dengue-related disease when successive infections of DENV take place. That is, someone already infected with Dengue once is likely to be asymptomatic, whereas if that person gets exposed to a different strain of DENV they are significantly more likely to suffer from Dengue Hemorrhagic Fever or Dengue Shock Syndrome. This does suggest that potentially ZIKV may be protective against DENV, which would need to be experimentally evaluated to determine the potential for these serious infections. Regardless of the approach, this research develops a unique lens for cross-reactivity of these flaviviruses and lends itself to further research to make use of this reactivity in potential vaccines to these serious and poorly understood diseases.

~Kyle Enriquez

Sources:

https://www.sciencedaily.com/releases/2019/02/190207142213.htm

http://science.sciencemag.org/content/363/6427/607

https://medicalxpress.com/news/2017-11-evidence-dengue-infection-severe-due.html