A Single-Dose Live-Attenuated Zika Virus Vaccine with Controlled Infection Rounds that Protects against Vertical Transmission

Zika virus (ZIKV) infection of the mother during pregnancy causes devastating Zika congenital syndrome in the offspring. A ZIKV vaccine with optimal safety and immunogenicity for use in pregnant women is critically needed. Toward this goal, we have developed a single-dose live-attenuated vaccine candidate that infects cells with controlled, limited infection rounds. The vaccine contains a 9-amino-acid deletion in the viral capsid protein and replicates to titers of > 10⁶ focus-forming units (FFU)/mL in cells expressing the full-length capsid protein. Immunization of A129 mice with one dose (10⁵ FFU) did not produce viremia, but elicited protective immunity that completely prevented viremia, morbidity, and mortality after challenge with an epidemic ZIKV strain (10⁶ PFU). A single-dose vaccination also fully prevented infection of pregnant mice and maternal-to-fetal transmission. Intracranial injection of the vaccine (10⁴ FFU) to 1-day-old mice did not cause any disease or death, underscoring the safety of this vaccine candidate. A ZIKV vaccine for use in pregnant women requires an optimal balance between safety and immunogenicity. Xie et al. developed a live-attenuated vaccine candidate that can infect cells with controlled, limited infection rounds. A single-dose immunization of the vaccine prevents vertical transmission of ZIKV in pregnant mice.