In the race to develop vaccines for the Zika virus, researchers faced an early hurdle that Canadian Gary Kobinger set out to overcome as swiftly as he could.
The challenge? Mice, the animals used in early tests of vaccine candidates, are too hardy to be sickened by the Zika virus.
So Dr. Kobinger genetically engineered a line of mice that would fall ill when exposed to Zika. Then, the Quebec-based microbiologist and his research partners in Philadelphia tested a DNA vaccine on the modified rodents, and, later, on rhesus macaques.
The experimental DNA vaccine, known as GLS-5700, shielded all the mice from Zika infection, brain damage and death, according to a new study published Thursday in the journal npj Vaccines. The vaccine also provoked a strong immune response in the monkeys; like wild mice, they are naturally resistant to Zika.
The findings are the first to be published in which a potential vaccine has been tested on animals susceptible to Zika, a mosquito-borne virus that has spread to more than 70 countries, including most of Latin America, the Caribbean and part of southern Florida, provoking worldwide concern because of its link to brain defects in newborns.
The hope is that a vaccine that shields pregnant women from Zika infection would protect their unborn children from microcephaly, too.
By one estimate, as many as 40 potential Zika vaccines are in early stages of development.
“[Dr. Kobinger and his partners] are the only group so far that’s actually reported to show protection of animals that get clinical [Zika] disease,” said Alan Barrett, the director of the Sealy Center for Vaccine Development at the University of Texas Medical Branch at Galveston. “It is important in terms of taking a vaccine forward … if they can protect animals against lethal infection, that’s much better than just protecting against virus in the blood.”
But Dr. Barrett, who was not involved in the research published Thursday, cautioned that when it comes to developing new vaccines, mice are a long way from humans.
“The problem is, does what happens in mice, happen in humans?” he asked. “There’s an old joke in science: Mice lie.”
Dr. Kobinger, the director of Laval University’s Infectious Disease Research Centre, and his research partner, David Weiner of the Philadelphia-based Wistar Institute, have already started tested their vaccine in people.
GLS-5700 became the first Zika vaccine to be approved for human safety trials in the United States and Canada in June.
Fourteen volunteers in Quebec City have already received two of three doses of the vaccine. The remaining 26 volunteers are receiving their shots in Philadelphia and Miami.
None of the subjects has suffered unexpected side effects, said Sylvie Trottier, the infectious disease specialist supervising the Quebec arm of the trial.
The GLS-5700 vaccine was also the first to move to human trials in a place where Zika is circulating, when a phase I trial with 160 participants kicked off in Puerto Rico at the end of August.
The double-blinded study, in which 80 Puerto Ricans will be injected with the real vaccine and another 80 will receive a placebo, is scheduled to run for a year, said Joseph Kim, the president of Inovio Pharmaceuticals, which is sponsoring development of the vaccine.
Dr. Weiner, the director of the Vaccine Center at the Wistar Institute, called the Puerto Rican trial a “very interesting and, possibly, very important and exciting,” step because, if the rate of Zika transmission in the territory is high enough, researchers could get a sense of whether the vaccine is effective in halting the spread of the virus.
Dr. Weiner specializes in DNA vaccines. He and Dr. Kobinger, who led development of the Ebola drug ZMapp in his last job as chief of special pathogens at the National Microbiology Laboratory in Winnipeg, are also testing DNA-based vaccines for Ebola and Middle East Respiratory Syndrome, or MERS. Both are in phase I human trials.
DNA vaccines work by injecting a molecule of DNA encoded to express a portion of a virus – in this case, Zika – tricking the immune system into mounting a defence.
No DNA vaccine for humans has made it to market yet, but Dr. Kobinger is bullish on the model.
“[DNA vaccines] are very stable. They’re the cheapest platform that I know, meaning making those vaccine doses is very cheap so it makes it affordable for developing countries,” he said. (Dr. Kobinger does not have a financial stake in GLS-5700. Dr. Weiner is on the board of Inovio Pharmaceuticals.)
Zika virus is spread primarily by Aedus aegypti mosquitoes, but it can also be transmitted through sex. In Canada, where the mosquito doesn’t normally circulate, the Public Health Agency of Canada has logged 359 travel-related cases of Zika, two sexually transmitted cases and two reports of maternal-to-fetal transmission as of Nov. 3.Report Typo/Error