Most vaccines aim to trigger protective antibodies. But for Zika, antibodies come with a catch — and researchers have now shown a way around it, using T cells instead.
Scientists at the La Jolla Institute for Immunology, led by Sujan Shresta, built an experimental Zika vaccine designed to protect primarily through CD8+ T cells rather than neutralizing antibodies. The reason: Zika closely resembles dengue, and cross-reactive antibodies can sometimes worsen a subsequent dengue infection — a phenomenon called antibody-dependent enhancement (ADE). A T-cell-based defense avoids that liability. The work was published in Nature Microbiology.
How they did it
The team introduced mutations in the virus’s envelope protein “fusion loop” — the region that normally generates cross-reactive antibodies. The mutated vaccine eliminated antibody protection but kept T-cell defense. In mice, CD8+ T cells from vaccinated animals alone reduced Zika levels when transferred to unvaccinated ones, and transferring antibodies from the mutant vaccine provided no protection — proof the defense was T-cell-driven.
Why it matters — and the caveat
“This vaccine wasn’t protecting via antibodies. It was protecting via T cells,” Shresta said. That’s an important proof of concept for regions where Zika and dengue circulate together. The trade-off: the T-cell protection was less durable, fading within about 12 weeks in mice, so durability would need to be solved. This is early preclinical research.