BY TRISTAN MAÑALAC
As athletes from all over the world flock to South America for the 2016 Rio Olympics, several experts have raised concerns about the safety of these athletes, particularly the females, in the face of the Zika outbreak. Continental USA has also seen its first outbreak in Florida, with now at least 16 confirmed cases that were contracted from local mosquitoes. These events further cement the pressing need for vaccines that are able to potently protect against Zika infections.
Three promising Zika vaccine candidates have cleared pre-clinical studies in both mouse and non-human primate animal models, scientists report in a recent publication in Science. Scientists from the Walter Reed Army Institute of Research, the Beth Israel Deaconess Medical Center, and the Harvard Medical School have shown that purified inactivated Zika virus vaccines, adoptive transfer of immunoglobulins, and plasmid DNA vaccines were all able to protect Rhesus monkeys from Zika virus infections.
In their trials, the team immunized a total of16 rhesus monkeys with the purified inactivated Zika virus (ZIKV PIV). Half of the monkeys received the ZIKV PIV vaccine with an alum adjuvant while the other half received a sham vaccine treatment.
Only the half immunized with the PIV produced ZIKV-neutralizing antibodies, the researchers found. When they challenged the monkeys with both the Brazil and Puerto Rico strains of the Zika virus, they found that the sham-treated monkeys experienced viremia for about a week while the PIV-immunized monkeys had no detectable viruses in their fluid secretions.
A previous study involving a strain of the Zika virus isolated from a site in Brazil has elucidated its genome to be one long linear RNA which encodes a polyprotein with a single reading frame. The genome is organized in such a way that structural proteins are clustered toward the 5’ end while the non-structural proteins are toward the 3’ end.
Using these sequence information, the research team designed a plasmid DNA vaccine which expressed the Zika pre-membrane envelope as an antigen, and proved its protective effects on mouse models. In the present study, they immunized monkeys with the plasmid DNA vaccine, a sham vaccine, or a rhesus adenovirus vector expressing the pre-membrane envelope.
They found that both the plasmid DNA vaccine and the vector vaccine were able to induce the production of anti-Zika antibodies and protect the monkeys from subsequent Zika infections. Between the two, however, the vector vaccine produced a stronger and broader immune response.
The team also investigated whether adoptive transfer of Zika vaccine-induced immunoglobulins (IgG, specifically) offered protection from future infections. They purified the IgG from PIV-immunized monkeys then transfused them into two groups of naïve rhesus monkeys with one group receiving a higher dose.
In the group that received the higher dose, one monkey experienced a slight viremia for three days while the group that received the lower dose didn’t show enhanced viral replication. These imply that adoptive transfer of purified IgG can confer passive protection from Zika.
Overall, the research team is hopeful that their vaccine candidates will enter the phase I clinical trials later this year and that their findings will further the search for safe and effective Zika vaccines.
More information about the studies, genome structure, and vaccine candidates can be found here: