Two vaccines protect against Zika virus infection in mice [PreClinical]

1. A DNA vaccine and a purified inactivated vaccine (PIV) conferred complete immunity in mice challenged with the Zika virus (ZIKV).

2. Purified IgG antibodies from the serum of DNA-vaccinated mice provided protection against ZIKV in naïve mice in a dose-dependent manner.

Evidence Rating Level: 2 (Good)

Study Rundown: Infection with ZIKV, the cause of a current global health crisis, has been associated with devastating consequences including fetal neurological disorders, intrauterine growth restriction, and microcephaly. In this work, the authors presented compelling evidence supporting the efficacy of two ZIKV vaccines in mice.

The plasmid DNA vaccine was developed based on the sequence of the full-length pre-membrane and envelope (prM-Env) of ZIKV originating from Brazil (ZIKV-BR). A single intramuscular (i.m.) injection of the vaccine four weeks before challenge with ZIKV-BR or ZIKV originating from Puerto Rico (ZIKV-PR) led to complete protection up to 6 days after infection. Mice that received two doses of DNA vaccine before ZIKV-BR challenge developed even higher levels of ZIKV-specific antibody titers. To explore the efficacy of an inactivated virus vaccine, a PIV derived from the ZIKV-PR strain was generated. Compared to the susceptible control group, mice vaccinated with the PIV via the i.m. route were completely protected from ZIKV-BR. To investigate the immunological mechanism that was responsible for protection, purified IgG antibodies were taken from serum from DNA-vaccinated mice. Unvaccinated animals that received intravenous transfusion of mid-range to high doses of ZIKV-specific antibody titers exhibited undetectable levels of ZIKV.

This work was among the first to present efficacious strategies for developing vaccines against ZIKV. Though the data are promising, future studies will be necessary to determine the clinical efficacy of these vaccinations against ZIKV in humans. Additionally, more long-term studies will need to assess the ability for these vaccines to provide lasting protection against ZIKV infection and its associated birth defects.

Click to read the study in Nature

Relevant Reading: Considerations for the development of Zika virus vaccines

In-Depth [animal study]: The DNA vaccine encoding for the prM-Env of ZIKV-BR was generated by cloning the prM-Env sequence into the mammalian plasmid pcDNA3.1+, isolating and purifying plasmids, and confirming the sequence using double stranded sequencing.  Balb/c mice were vaccinated with the 50 μg of DNA via i.m. injection four weeks before being infected with 10⁵ viral particles of ZIKV-BR or ZIKV-PR. While sham-vaccinated animals developed a mean peak viral load of 5.42 log copies/mL and 4.96 log copies/mL of ZIKV-BR (n=10) and ZIKV-PR (n=5), respectively, the DNA-vaccinated group exhibited undetectable levels of ZIKV-BR (n=10) and ZIKV-PR (n=5) for six days after infection. Mice that received two doses of DNA vaccine four weeks apart were also protected from ZIKV-BR and developed high levels of ZIKV-neutralizing antibody titers (50% microneutralization titer=1,022).

The PIV was generated by treatment of the ZIKV-PR with formalin for seven days. Once purified, 1 μg of the PIV was intramuscularly administered. Four weeks after vaccination, mice were challenged with ZIKV-BR. Similar to the group treated with the DNA vaccine, the PIV-treated group (n=5) experienced complete protection from ZIKV for up to six days after infection.

Finally, IgG antibodies were collected from the serum of DNA-vaccinated mice and delivered to naïve recipient mice. Mice that received at least 2.35 log copies of Env-specific antibody titers were protected from ZIKV infection. Only one out of five recipient mice that received low levels of titers was protected whereas the remaining four showed detectable viremia, though their viral loads were reduced compared to the sham condition.

Image: PD

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