Volz Asisa, Clever Sabrina, Tscherne Alina, Freudenstein Astrid, Jany Sylvia, Schwarz Jan H, Limpinsel Leonard, Valiant William G, Kalodimou Georgia, Sutter Gerd, Mattapallil Joseph J
Institute of Virology, University of Veterinary Medicine Hannover, Hannover, Germany.
Division of Virology, Department of Veterinary Sciences, LMU Munich, Munich, Germany.
NPJ Vaccines. 2025 Mar 5;10(1):44. doi: 10.1038/s41541-025-01094-0.
Zika virus (ZIKV) outbreak of 2015 was associated with microcephaly and congenital birth defects in children born to pregnant women infected with ZIKV. Using the highly susceptible Type I Interferon Receptor-deficient mouse-model, we demonstrate that a single emergency vaccination with a non-replicating MVA-ZIKV vaccine, when administered as early as 2-days before challenge fully protected non-pregnant and pregnant mice and fetuses against lethal ZIKV-infection. Early protection was associated with the rapid emergence of ZIKV-specific CD8+ T cell responses; depletion of CD8+ T cells resulted in the loss of protection supporting a critical role for CD8+ T cells in the early protective efficacy of MVA-ZIKV. Neutralizing antibody responses were induced later than the CD8+ T cell responses, suggesting that it may play a role in later stages of infection. Our results suggest that MVA-ZIKV induces potent anamnestic cellular immunity early after infection, contributing to its protective efficacy against rapid ZIKV challenge.
2015年寨卡病毒(ZIKV)疫情与感染ZIKV的孕妇所生儿童的小头畸形和先天性出生缺陷有关。利用高度易感的I型干扰素受体缺陷小鼠模型,我们证明,早在攻击前2天给予一次非复制型MVA-ZIKV疫苗进行紧急接种,就能完全保护未怀孕和怀孕的小鼠及胎儿免受致命的ZIKV感染。早期保护与ZIKV特异性CD8 + T细胞反应的迅速出现有关;CD8 + T细胞的耗竭导致保护作用丧失,这支持了CD8 + T细胞在MVA-ZIKV早期保护效力中起关键作用。中和抗体反应比CD8 + T细胞反应诱导得晚,这表明它可能在感染后期起作用。我们的结果表明,MVA-ZIKV在感染后早期诱导强烈的记忆性细胞免疫,有助于其对快速ZIKV攻击的保护效力。