Vaccine against Zika virus tested successfully in mice
Agência FAPESP/DICYT An experimental vaccine against Zika virus developed by Brazilian and US researchers has been tested successfully in trials with mice. The results were published on June 28 in Nature and according to the authors suggest a vaccine can be produced for humans in the near future.
In Brazil the trials were performed under the aegis of the Zika Virus Research Network in São Paulo (Rede Zika), with FAPESP’s support, and coordinated by Jean Pierre Peron and Paolo Zanotto, both affiliated with the University of São Paulo’s Biomedical Science Institute (ICB-USP). In the US the coordinator was Harvard University’s Dan Barouch, a vaccine design expert. One of the first authors is Rafael Larocca, a former student at ICB-USP’s Immunology Department and former awardee of a scholarship from FAPESP.
“The vaccine gave the mice 100% protection,” Person said. “In other words, they were vaccinated and then infected, and didn’t present viremia,” meaning plasma viral load was equal to zero and the infection did not progress.
The vaccinated animals were challenged both with a strain of the virus originating in Puerto Rico and with a Brazilian strain, isolated from a baby born in Paraíba State and used in previous research by Rede Zika. Also published in Nature, the prior study confirmed the causal link between infection by Zika virus and microcephaly.
In both cases the vaccine induced a protective immune response. The group of mice that received placebo instead of the vaccine presented with viremia for a period of five or six days after being infected.
“We isolated the antibodies produced in the organisms of the vaccinated mice and transferred them to other mice. So these mice received antibodies ready-made, as it were. They were then infected and also proved resistant, demonstrating that the vaccine induces antibody-mediated protection,” Peron said.
Constructing the vaccine
Several combinations of viral antigens – proteins from Zika virus capable of inducing an immune response – were tested. The best results were yielded by prM (premembrane protein) combined with Env (external envelope protein).
The antigens were inserted into a plasmid, a small circular DNA molecule. According to Peron, the same kind of formulation can be used in human trials.
“One more preclinical trial is still required, this time involving monkeys. If this also has positive results, we can begin Phase I clinical trials,” he said.
First, however, the group will test the vaccine further in mice to find out if it protects fetuses against the development of microcephaly during gestation.
“My students are going to Dan Barouch’s lab in the US to perform these experiments with pregnant female mice,” Peron explained. “If we can indeed protect fetuses against microcephaly, it will be a very promising outcome. And we’re prepared to wager that will happen.”
The article “Vaccine protection against Zika virus from Brazil” (doi: 10.1038/nature18952) can be read at nature.com/nature/journal/vaap/ncurrent/full/nature18952.html.