Manifestations of Zika virus (ZIKV) infection differ drastically. Sometimes they are catastrophic, most notably when they cause microcephaly in some babies born to infected mothers. At other times, they are mild and fleeting, suggesting that unknown factors temper Zika infections’ severity.
Recently, dengue virus emerged as a prime suspect because it shares many genetic and structural characteristics with ZIKV and is endemic in most of the regions affected by Zika’s global spread.
Mice rendered immune to dengue show “cross-protection” from subsequent Zika infection and then identifies specific types of immune T-cells capable of defending against both viruses.
These revelations have profound implications for efforts to build a potent anti-Zika vaccine. 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. Vaccines targeting either virus could be engineered to induce both T cell and antibody responses effective to protect people in these areas.
When one encounters a pathogen in real life, two arms of the immune system spring into action to neutralize it. In the so-called humoral response, B-cells begin to secrete specific antibody proteins, which latch onto and neutralize pathogens in tissue or blood. Simultaneously, a cell-mediated immunity system also becomes active, deploying cytotoxic T-cells to directly recognize and kill pathogen-infected cells.
The ideal vaccine might mimic both antibody and T cell responses to block an infectious disease. But in truth, most (26 of 28 vaccines currently licensed for human use) stimulate primarily a B-cell or antibody response, which in many cases is sufficient. Reseache team created the first “sequential” mouse model mimicking dengue-then-Zika infection. To do that, they infected mice genetically vulnerable to this family of viruses with dengue virus.
Those mice became sick, recovered from infection, and hence acquired immunity to dengue, presumably because viral infection had mobilized their immune B-cells, T-cells or both. The group then inoculated the same mice with ZIKV and waited to see if mice showed ZIKV symptoms. But overall, mice that had previously acquired dengue immunity showed protection against Zika, as evidenced by a reduced burden of ZIKV in blood and tissues, such as brain, liver or testis, compared to control mice not “pre-inoculated” against dengue.
These experiments suggest that the reason that some people infected with Zika do not come down with disease is due to prior exposure to dengue. This may explain why Zika is not passed to the unborn child of every pregnant woman in dengue-endemic countries exposed to virus. In a different experiment, the scientists isolated cytotoxic T cells from the blood of dengue-immune mice and infused them into normal mice, a procedure known as adoptive T-cell transfer.
When infused mice were then infected with ZIKV, they also showed disease resistance, supporting the idea that the T-cell arm of the immune system can do the heavy lifting against ZIKV infection. A successful vaccine would need to include components to induce not only a B-cell response but also a T-cell response.