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Zika Vaccine Mutant Protects Mice Through T Cells but Immunity Wanes

The finding shows CD8+ T cells can clear Zika infection in mice and offers a route to vaccines that avoid cross-reactive antibody risks.

Overview

  • The study, published Aug. 26, 2026, reported that a Zika vaccine engineered with mutations in the E protein fusion loop protected mice by activating CD8+ T cells rather than by producing neutralizing antibodies.
  • Antibodies from the fusion-loop mutant looked similar to normal vaccine antibodies in lab tests but failed to protect animals when transferred to unvaccinated mice, showing they did not provide passive immunity.
  • When researchers transferred CD8+ T cells from vaccinated mice into unvaccinated animals those cells reduced Zika levels, and removing CD8+ T cells from vaccinated mice erased protection, proving T cells were the key protective mechanism.
  • That T cell–mediated protection was short-lived: mice given the fusion-loop mutant lost protection by 12 weeks after vaccination while animals given the unmodified vaccine remained protected over the same interval.
  • Authors say the result could inform 'pan-orthoflavivirus' vaccines that avoid antibody-dependent enhancement—when cross-reactive antibodies make infections worse—but they caution that making T cell memory durable and translating mouse results to humans remain major challenges.