Experimental Zika vaccine protects mice through T cells alone

A vaccine protected mice from Zika even after researchers removed the role usually assigned to antibodies. At La Jolla Institute for Immunology, Sujan Shresta, Annie Elong Ngono and Kantinan Chuensirikulchai found that CD8+ T cells—immune cells that find and destroy infected cells—could drive protection on their own.

The finding tackles a problem that has held back Zika vaccines. Zika and dengue are close relatives, with similar outer envelope proteins. Antibodies trained on one virus can bind the other without disabling it, a phenomenon called antibody-dependent enhancement, or ADE, that can ferry the virus into immune cells and worsen infection. The researchers therefore compared two experimental vaccines in mice: one with natural outer proteins, and one with a mutated fusion loop, the region linked to many cross-reactive antibodies.

The unmodified vaccine protected through both antibodies and T cells. Transferring CD8+ T cells from vaccinated mice into unvaccinated animals lowered Zika levels, showing that the cells were doing more than supporting the antibody response. The fusion-loop mutant produced a sharper result: its antibodies resembled those from the other vaccine in cell cultures and test tubes, but did not protect unvaccinated animals. Removing the CD8+ T cells erased the protection.

And concretely? The approach could give researchers a route to protect against Zika without relying entirely on antibodies that might create ADE risks around dengue and related viruses. That matters for populations exposed to a virus reported in at least 97 countries and territories, including pregnant women, for whom Zika infection has been linked to congenital Zika syndrome. But this is still a mouse result, not a human vaccine.

The central limitation arrived with time. Twelve weeks after the final dose, mice that received the fusion-loop mutant were no better protected than unvaccinated animals, while those given the unmodified vaccine remained protected. Shresta's team is now investigating how to build a more durable T-cell response; the source does not yet provide a human trial, product or deployment timetable.