UNC bioethicist pens ‘cautionary tale’ for Zika vaccine development and pregnancy

UNC’s Anne Lyerly, MD, published an opinion piece in JAMA Pediatrics that urges scientists to use lessons learned during the Rubella outbreak as they work to develop a vaccine for the Zika virus, specifically as it relates to the ethics of including pregnant women in vaccine trials.

UNC bioethicist pens ‘cautionary tale’ for Zika vaccine development and pregnancy click to enlarge Anne Lyerly, MD

June 26, 2017

Media contact: Matt Englund, matthew.englund@unchealth.unc.edu, (919) 923-2347

CHAPEL HILL, NC –  As scientists develop a vaccine for the Zika virus, a UNC bioethicist is working to ensure that pregnant women are represented in the Zika vaccine development agenda.

Anne Lyerly, MD, associate director of the UNC Center for Bioethics and professor of social medicine at the UNC School of Medicine, is an obstetrician/gynecologist who studies ethically complex clinical and policy issues related to women’s reproductive health. Lyerly is part of a Wellcome Trust-funded interdisciplinary team with colleagues at Georgetown University and Johns Hopkins Berman Institute of Bioethics. The team, tasked with focusing on the ethics and research in pregnancy and women of reproductive age, is poised to release to the scientific community its recommendations for including pregnant women in the Zika research agenda.

In a commentary published today in JAMA Pediatrics, Lyerly shared her thoughts on Zika vaccine development, which is underway at multiple medical and scientific institutions across the country, including at UNC, and what researchers can learn from lessons in dealing with a similar virus – Rubella.

“Rubella has emerged in many conversations around Zika, because like the Zika virus, Rubella causes a mild illness in adults, but causes terrible congenital malformations in children,” Lyerly explained. “People were really looking to this as the paradigm case in history where we’ve seen this before.”

The Rubella vaccine is generally considered a success story since the virus was largely eradicated in the Americas in the 1980s, but Lyerly cautions that perhaps it wasn’t quite the win the scientific community once thought.

“When I was looking at this history from a 40,000-foot view, I realized there was very little conversation about vaccinating pregnant women, who, of course, are the very people we most wanted to protect from Rubella. When the Rubella vaccine was first developed, it was a live vaccine, which is generally not used in pregnant women, except in very rare cases because people think there is a risk in infecting a fetus with a live vaccine.”

At the time, research showed that the live virus could get to the fetus, but it never presented any harm.

“Until the very recent past, people first developed vaccines, then only later considered whether they could be used in pregnant women,” Lyerly said. “Part of what I thought would be interesting would be to think about how people did this in the past – what kind of policies were around, what thinking reflected those policies and what were the results.”

During the 1980s, plans called to vaccinate around the people most at risk, which at the time in the U.S., were preschool and school-age children. The thought being that if the children were protected, then the mothers and other women of childbearing age would be, as well. But that’s not what happened.

“This is a story that people really don’t talk about that much,” Lyerly said. “They were trying to protect pregnant women by keeping the vaccine away from them. Instead, there was more Rubella in them. Because the Rubella wasn’t infecting the children, it was concentrating in the non-vaccinated population, which is what scientists call the paradoxical effect. This was a really important lesson of Rubella.”

When organizations like the Centers for Disease Control and Prevention and the American Academy of Pediatrics recognized this, they extended the vaccine to women of childbearing age, Lyerly said.

“In less than a decade, it was all but eradicated in the Americas,” she said. “This was an important move because people had to be brave. What they knew is that if you vaccinate women of childbearing age, some of those women will get pregnant. In the early days, nobody had really studied the live Rubella vaccine, so they didn’t really know if it was harmful.

“In general, when women who were vaccinated became pregnant, at least half of those women terminated their pregnancies – maybe more because of underreporting. Many of those were desired pregnancies, which, to me, is a tragedy in itself. It turns out, over time, people who did not terminate pregnancies were followed and the babies were followed, and from what we can tell there has never been a case reported of congenital Rubella disease from a Rubella virus. We dug and we dug and we couldn’t find a link between congenital Rubella disease and the live vaccine.”

Today in the U.S., pregnant women are tested for a Rubella immunity. If a woman is not immune to Rubella, she will be given a Rubella vaccine postpartum, Lyerly said.

“When it comes to research and pregnant women, many scientists think, ‘better safe than sorry,’ because they don’t want to expose pregnant women to unnecessary risk in the context of the study. But the refusal to consider the interests of pregnant women in the research and development agenda – medicines, vaccines – does not necessarily protect them, but, in fact, puts them in harm’s way.”

“Caution is a double-edged sword in some ways. I also think it really highlighted the fact that if you don’t have data for things, it doesn’t necessarily protect because of the worry that comes from uncertainty. Women who are exposed to drug or vaccines who don’t have any evidence about safety, may terminate that pregnancy, so that doesn’t make that pregnancy any safer.”

In addition to interviewing researchers and scientists in relation to vaccine development, the team has partnered with Harvard University on a study that includes interviewing women who have had Zika, and soliciting their opinions on what forms of vaccines they would have considered during pregnancy.

“We have really pushed this notion that you can’t just think about vaccinating around pregnant women and hoping they’re going to be protected from Zika. The vaccine community has recognized that and they have identified women of childbearing age as the target demographic for the Zika vaccine,” she said.

Another reality about the Zika virus and its most vulnerable targets is that, particularly in the parts of the world where Zika is most prevalent, many women won’t seek healthcare until they are pregnant.

“For these women, their only opportunity to be protected from Zika is going to be when they are pregnant,” Lyerly said. “We know from prior epidemics that if you vaccinate women of childbearing age, some of them are going to get pregnant. And they’re going to want to know if the vaccine is safe and if the vaccine is efficacious.

“Rubella is a reminder that it’s not such a success story, and you have to be brave and look at how to ethically involve pregnant women in the process going forward rather than figuring things out retrospectively.”

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