Two separate animal studies today filled in more information gaps about Zika virus: one on rhesus monkeys that yielded new clues about infection during pregnancy, and one in mice showing encouraging results for two vaccine candidates.
The primate study, by a team from the University of Wisconsin-Madison and Duke University, appeared in Nature Communications. And the mouse findings were reported by a large research group that included scientists from Beth Israel Medical Center, the National Institute of Allergy and Infectious Diseases (NIAID), and the Walter Reed Army Institute of Research (WRAIR) who published their results in Nature.
Monkey study
The findings from rhesus macaque monkeys is part of ongoing work to study Zika infection in the animals—looking for clues on how it might affect humans—at the Wisconsin National Primate Research Center. The study included eight animals, two of them pregnant.
In their report, the investigators revealed that monkeys infected with the Zika strain currently circulating in South America can resist infection when challenged by the same strain 10 weeks later. The team said the immune system priming from an earlier infection might explain why birth defect outcomes haven't been seen in Africa, where the virus has circulated for many years.
The more startling finding was dramatically longer infections in pregnant animals. Monkeys that weren't pregnant typically cleared the virus within 10 days of infection, but virus persisted in the blood of the pregnant ones from 30 to 70 days, according to the study.
Emma Mohr, MD, PhD, pediatric infectious disease fellow and study first author, said in a UW-Madison press release, "What we've shown in the monkey model matches a lot of what people have observed in epidemiological studies of humans."
The immunity findings bode well for vaccine design, David O'Connor, PhD, a pathology professor who led the study, said in the press release. It suggests the sort of immunity that occurs naturally is sufficient. If you can mimic that in a vaccine, you'll likely have a very successful vaccine."
Virus activity in pregnancy
Prolonged Zika infection during pregnancy might play a role in severe complications to fetuses, and O'Connor said his concern about the link to the virus is higher now than it was 6 months ago. Researchers said maternal immune compromise during pregnancy could explain the persistence, but experts are considering another possible mechanism: that prolonged maternal Zika virus levels might reflect viral shedding from the fetus back into the mother's bloodstream.
If the second possibility holds true, clinicians might be able to monitor Zika load in the blood of pregnant women weekly or biweekly as a way to gauge possible damage to their babies, O'Connor said in the statement.
The team is monitoring the pregnant Zika-infected monkeys with ultrasound and tests on amniotic fluid, but so far they can't tell if the fetuses are infected or if they have any birth defects such as microcephaly.
Vaccine candidates perform well in mice
Meanwhile, scientists involved in the mouse study tested two vaccine candidates: a DNA vaccine developed at Beth Israel Deaconess Medical Center based on the strain circulating in Brazil and a purified inactivated vaccine developed at WRAIR based on Zika virus from Puerto Rico.
A single shot of vaccine protected all mice challenged with the virus 4 weeks later and those experimentally exposed to Zika virus 8 weeks later. The teams also found that antibody levels seemed to correlate with protection against the disease.
Experiments involving the DNA vaccine suggested that protection was solely from antibodies prompted by the vaccine.
Taken together, the findings offer great hope that a safe and effective vaccine for humans will one day be feasible, the group wrote.
Stage set for first human trials
Col. Stephen Thomas, MD, with the WRAIR Zika program, said in a press release from the US Military HIV Research Program (MHRP) that their group is moving forward with the purified inactivated vaccine because it is similar to vaccines that have already been licensed and involves technology the group has used to successfully develop other flavivirus vaccines.
"Researchers are trying to mitigate risk by avoiding unproven technologies that could cause a licensing delay," he added.
WRAIR also has in-house production capacity that allowed them to make small batches of vaccine for the mouse study, with production under way on a vaccine lot for use in initial human studies that are expected to launch by the end of the year. The first human trials of the DNA vaccine tested in the study are also expected to begin by the end of the year.
In February, Inovio reported promising preclinical findings in mice for a candidate DNA vaccine against Zika virus that it is developing with partners including GeneOne Life Sciences. The Food and Drug Administration recently cleared the launch of that vaccine's phase 1 study in humans, expected to begin in the next few weeks with initial results later this year.
See also:
Jun 28 Nat Comm abstract
Jun 28 UW-Madison press release
Jun 28 Nature abstract
Jun 28 MHRP press release
Jun 28 NIAID press release
Jun 28 Beth Israel Deaconess Medical Center press release
Feb 16 CIDRAP News story "Inovio reports promising Zika vaccine results in mice"
