Could T cell immunity from dengue infection protect against Zika?

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It has been noted that Zika infection can result in a huge range of manifestations, suggesting that many unknown factors may temper the virus’s severity. New research has addressed the interaction between dengue and Zika, reporting that mice with dengue immunity demonstrate cross-protection from subsequent Zika infections.

Dengue’s interaction with Zika virus has been the subject of debate, as a result of genetic and structural similarities. This study, published in Nature Communications, reveals a dual dengue/Zika immunity conferred by cytotoxic T cells capable of defending against both viruses, and its findings could have implication in the efforts for an anti-Zika vaccine.

Author Sujan Shresta (La Jolla Institute, CA, USA) commented: “In some parts of the world Zika is almost like a secondary infection. It has spread into Brazil/Latin America and is moving into places in Asia where people previously had dengue. Our new work suggests that vaccines targeting either virus could be engineered to induce both T cell and antibody responses effective to protect people in these areas.”

The researchers developed the first sequential mouse model, mimicking dengue then Zika infections via timed inoculations with these viruses. They observed that mice with previously acquired dengue immunity possessed protection against Zika infection, with reduced viral load in both blood and tissues.

Researchers also isolated cytotoxic T cells from dengue-immune mice, infusing them into controls in a procedure termed adoptive T cell transfer. When infused mice were subsequently infected with Zika, they too demonstrated protection, supporting idea that the T cell response is critical.

Most vaccines only stimulate an antibody response, which is often sufficient; however, this research suggests that protection against thus far intractable pathogens may require both T cell and B cell responses. The team suggest that optimization of the current dengue vaccines for T cell responses might confer cross-protection, preventing antibody-mediated enhancements of Zika infection.

First author, Jinsheng Wen (Wenzhou Medical University, Wenzhou City, China) explained: “Our work strongly suggests that a successful vaccine would need to include components to induce not only a B cell response but also a T cell response.”

Shresta concluded: “Approved vaccines for many diseases work by inducing antibody responses. But now we are dealing with problematic diseases, like dengue and Zika for which we cannot rely solely on raising antibodies. Certain pathogens are likely to also require a T cell response.”

Sources: Wen J, Ngono AE, Regla-Nava JA et al. Dengue virus-reactive CD8+ T cells mediate cross-protection against subsequent Zika virus challenge. Nat. Comms. doi:10.1038/s41467-017-01669-z (2017); www.eurekalert.org/pub_releases/2017-11/ljif-dic110817.php

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