Mouse model to aid Zika vaccine testing

Researchers have established a new mouse model for testing vaccines and therapeutics to fight the Zika virus.

The new model is able to mimic aspects of the human infection, with infection occurring via the skin as it would through a mosquito bite. According to the researchers, previous models dating back to 1976 weren’t as clinically relevant as the infection was generated by injecting the virus directly into the brain.

Mice can be immunized with a candidate vaccine and then challenged,” Michael Diamond, MD, PhD, at Washington University School of Medicine, told Outsourcing-Pharma.com. “Viremia, clinical morbidity, viral burden in tissues, and mortality can be followed.”

After infection the mice with the virus, researchers saw high levels of the virus in the brain and spinal cord, which is in line with evidence the shows Zika causes neurological defects in human fetuses. Additionally, the hypothesis that the virus can be sexually transmitted was supported, as the highest levels of the virus were detected in male testes.

"We looked for evidence of Zika in the mouse testes mostly as an afterthought, due to mounting evidence of sexual transmission and were surprised that viral levels were the highest we saw in any tissue," said Diamond. The researchers are currently doing further tests to determine how long these levels are sustained in order to help estimate the length of time Zika can be transmitted sexually.

Five Zika virus strains were tested in total, with all yielding similar results. Diamond told us, it took “intensive study of many different mouse lines to find the one(s) that recapitulated human disease.”

The researchers used animals that were genetically altered so that they couldn’t produce interferon, which dampens the immune system’s response to the virus.

"If you take away interferon, the Zika virus replicates quite well in the mouse and goes to the sites that we see it causing disease in humans," said Diamond, who is a professor of molecular microbiology and of pathology and immunology.

According to the researchers, the genetically engineering mice lost weight, became lethargic, and died within 10 days of infection. On the contrary, normal laboratory mice only developed symptoms if they were infected soon after birth, before their immune systems were fully developed.