Both Dengue and Zika viruses are mosquito-borne viral infections transmitted by a bite from mosquitoes of the Aedes aegypti species in tropical and sub-tropical climates. Recent estimates indicate 390 million dengue infections per year, with 96 million manifesting clinically, and 3.9 billion people in 128 countries at risk for disease. A total of 86 countries and territories have reported evidence of mosquito-transmitted Zika infection, with over 5,000 cases reported in the United States and over 35,000 reported in US Territories since 2016. A recent study published in Nature Communications looks at the connection between previous Dengue infection and immunity and Zika infection during pregnancy.
During pregnancy, Zika virus can be transmitted from mother to fetus, which can lead to congenital malformations such as microcephaly in infants and occurs in both asymptomatic and symptomatic cases. These malformations are collectively referred to as congenital Zika syndrome and can affect muscle tone, eyes, hearing, and limb contractures. The risk for congenital disabilities following infection in pregnancy is unknown, but 5-15% of infants born to women infected with Zika virus during pregnancy have evidence of Zika-related complications.
Dr. Sujan Shresta, of the La Jolla Institute for Allergy and Immunology, utilized mouse models to observe the effects of Dengue immunity in pregnant mothers on Zika-related malformations in infants. A previous study done by the group showed that Dengue-infected adult mice exhibit protection against Zika infection. Protection is due to cross-reactive CD8+ T cells, immune cells essential to the adaptive immune response, targeting Zika. To further explore cross-protection female mice with Dengue immunity were impregnated and exposed to Zika virus at an early embryonic stage to see if immunity shielded the fetus as well as the mother from zika-related damage. Fetuses of dengue-immune mice appeared normal compared to dengue-naïve controls, to the point that many were indistinguishable from fetuses never exposed to Zika.
Further investigation revealed that the CD8+ T cells created from Dengue infection were present at the maternal/placental border of Zika-infected pregnant mice, creating a potential line of defense against transmission. When the T cells were eliminated fetuses became vulnerable to Zika infection and fetal cell destruction. To probe the abilities of Dengue infection to provide immunity, Dengue naïve mice were exposed to dengue virus peptides, short proteins, known to induce T cell response. Exposure simulated a vaccine scenario and decreased Zika infection in fetuses of pregnant mice exposed to the vaccine compared to unvaccinated mice. The T cell response was effective in this scenario without actual Dengue infection.
Currently, both Zika and Dengue vaccines under development elicit primary antibody (B cell) responses instead of T cell responses with only moderate success in conveying protection. "Dengue and ZIKV are carried by the same mosquitoes, co-circulate in overlapping geographic ranges, are structurally related, and evoke cross-reactive antibody and T cell responses," says Jose Angel Regla-Nava, Ph.D., a postdoctoral fellow in the Shresta lab and a co-lead author. "Both antibody and T cell responses together may be required for protection against these infections." Creating vaccines that elicit T cell responses can be challenging, but new technologies and these results encourage that approach as a useful vaccine option against a growing public health crisis. Dr. Shresta says that future studies will focus on boosting the period of cross-protection between Dengue immunity and Zika, to confer longer lasting protection.
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WHO Dengue, WHO Zika, CDC
