A systematic approach to the development of a safe live attenuated Zika vaccine

作者：Sen Kwek Swee; Watanabe Satoru; Chan Kuan Rong; Ong Eugenia Z; Tan Hwee Cheng; Ng Wy Ching; Nguyen Mien T X; Gan Esther S; Zhang Summer L; Chan Kitti W K; Tan Jun Hao; Sessions October M; Manuel Menchie; Pompon Julien; Chua Camillus; Hazirah Sharifah; Tryggvason Karl; Vasudevan Subhash G; Ooi Eng Eong

来源：Nature Communications, 2018, 9(1): 1031.

DOI：10.1038/s41467-018-03337-2

Zika virus (ZIKV) is a flavivirus that can cause congenital disease and requires development of an effective long-term preventative strategy. A replicative ZIKV vaccine with properties similar to the yellow fever 17D (YF17D) live-attenuated vaccine (LAV) would be advantageous, as a single dose of YF17D produces lifelong immunity. However, a replicative ZIKV vaccine must also be safe from causing persistent organ infections. Here we report an approach to ZIKV LAV development. We identify a ZIKV variant that produces small plaques due to interferon (IFN)-restricted viral propagation and displays attenuated infection of endothelial cells. We show that these properties collectively reduce the risk of organ infections and vertical transmission in a mouse model but remain sufficiently immunogenic to prevent wild-type ZIKV infection. Our findings suggest a strategy for the development of a safe but efficacious ZIKV LAV.

• 出版日期2018-3-12