A single-dose plasmid-launched live-attenuated Zika vaccine induces protective immunity

BACKGROUND: Vaccines are the most effective means to fight and eradicate infectious diseases. Live-attenuated vaccines (LAV) usually have the advantages of single dose, rapid onset of immunity, and durable protection. DNA vaccines have the advantages of chemical stability, ease of production, and no cold chain requirement. The ability to combine the strengths of LAV and DNA vaccines may transform future vaccine development by eliminating cold chain and cell culture with the potential for adventitious agents. METHODS: A DNA-launched LAV was developed for ZIKV virus (ZIKV), a pathogen that recently caused a global public health emergency. The cDNA copy of a ZIKV LAV genome was engineered into a DNA plasmid. The DNA-LAV plasmid was delivered into mice using a clinically proven device TriGrid™ to launch the replication of LAV. FINDINGS: A single-dose immunization as low as 0.5 μg of DNA-LAV plasmid conferred 100% seroconversion in A129 mice. All seroconverted mice developed sterilizing immunity, as indicated by no detectable infectious viruses and no increase of neutralizing antibody titers after ZIKV challenge. The immunization also elicited robust T cell responses. In pregnant mice, the DNA-LAV vaccination fully protected against ZIKV-induced disease and maternal-to-fetal transmission. High levels of neutralizing activities were detected in fetal serum, indicating maternal-to-fetal humoral transfer. In male mice, a single-dose vaccination completely prevented testis infection, injury, and oligospermia. INTERPRETATION: The remarkable simplicity and potency of ZIKV DNA-LAV warrant further development of this vaccine candidate. The DNA-LAV approach may serve as a universal vaccine platform for other plus-sense RNA viruses. FUND: National Institute of Health, Kleberg Foundation, Centers for Disease Control and Prevention, University of Texas Medical Branch.