Vaccines protect unborn mice from Zika infection

Goldsmith/CDC

Researchers have reported that 2 different vaccines can protect mice from Zika virus-induced congenital disease.

Female mice that were vaccinated before pregnancy and infected with Zika virus while pregnant bore pups that showed no trace of the virus.

These results, published in Cell, offer the first evidence that a vaccine administered prior to pregnancy can protect fetuses from Zika infection and resulting injury.

“There are several vaccines in human trials right now, but, to date, none of them has been shown to protect during pregnancy,” said Michael S. Diamond, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri.

“We tested 2 different vaccines, and they both provided substantial protection.”

Last year, Dr Diamond and his colleagues developed a mouse model of Zika infection that mimics the effects of the infection in pregnant women.

Using this model, the researchers evaluated the ability of 2 vaccines to protect fetuses whose mothers were infected during pregnancy.

One of the vaccines is a messenger RNA (mRNA) vaccine, developed by Moderna Therapeutics, that is currently in safety testing in men and women who are not pregnant.

The other is a live-attenuated vaccine, developed by the University of Texas Medical Branch, that is being tested in animals.

For this study, groups of 18 to 20 female mice were vaccinated with one of the vaccines or a placebo, and some animals received a second dose of the same vaccine or placebo a month later.

Three weeks later, the researchers measured antibody levels in the mice’s blood as a measure of the strength of their immune response.

Both vaccines elicited very high levels of neutralizing antibodies against Zika, while the placebos did not.

After the mice became pregnant, they were infected with Zika on the sixth day of pregnancy, to mimic the experience of a woman bitten by a Zika-carrying mosquito early in pregnancy.

One week after infection, the researchers measured the amount of virus in the mothers and fetuses.

With both vaccines, fetuses and placentas from vaccinated mice contained very low levels of Zika’s genetic material.

For the mRNA vaccine, more than half of the placentas and fetuses had no detectable viral genetic material at all.

The live-attenuated vaccine was even more effective. In 78% of the placentas and 83% of the fetuses, no viral genetic material was found.

“The amount of viral genetic material in the placentas and fetuses from the vaccinated females was just above the limit of detection,” Dr Diamond said. “It’s not totally clear whether it was infectious virus or just remnants of viruses that had already been killed.”

In contrast, the amount of detectable viral material in the placentas and fetuses of unvaccinated mice was hundreds to thousands of times higher.

The researchers repeated the experiment with different mice so they could evaluate the pups at birth.

None of the mothers in the placebo group made it to term. The mothers became seriously ill, many of the fetuses showed high levels of infection and died in utero, and the placentas showed severe damage.

In contrast, the vaccinated mothers remained healthy, all of their pups were born without obvious signs of injury, and the newborn pups had no measurable Zika virus in their heads.

“In general, most doctors don’t want to vaccinate during pregnancy on the outside chance that the immune response itself could harm the fetus,” Dr Diamond said. “But if you’re in an area where Zika is circulating, you might vaccinate during pregnancy because the risk of Zika infection is worse than some theoretical risk of immune-mediated damage.”

The researchers did not assess whether the vaccines are safe and effective for use during pregnancy.

Such studies couldn’t really be done in mice, Dr Diamond explained, because mouse pregnancies only last 19 days. That doesn’t allow enough time for a protective immune response to develop before the pups are born.

Additionally, this study did not address the question of whether the vaccines work when pregnant women are infected with Zika through sexual contact. It is possible that Zika virus in semen can travel to the uterus and then to the fetus without passing through the bloodstream.

“The question is, ‘Would the immunity still hold up if the virus does not pass through the bloodstream?’“ Dr Diamond said. “We think it will hold up, but that has to be tested.”

Goldsmith/CDC

Researchers have reported that 2 different vaccines can protect mice from Zika virus-induced congenital disease.

Female mice that were vaccinated before pregnancy and infected with Zika virus while pregnant bore pups that showed no trace of the virus.

These results, published in Cell, offer the first evidence that a vaccine administered prior to pregnancy can protect fetuses from Zika infection and resulting injury.

“There are several vaccines in human trials right now, but, to date, none of them has been shown to protect during pregnancy,” said Michael S. Diamond, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri.

“We tested 2 different vaccines, and they both provided substantial protection.”

Last year, Dr Diamond and his colleagues developed a mouse model of Zika infection that mimics the effects of the infection in pregnant women.

Using this model, the researchers evaluated the ability of 2 vaccines to protect fetuses whose mothers were infected during pregnancy.

One of the vaccines is a messenger RNA (mRNA) vaccine, developed by Moderna Therapeutics, that is currently in safety testing in men and women who are not pregnant.

The other is a live-attenuated vaccine, developed by the University of Texas Medical Branch, that is being tested in animals.

For this study, groups of 18 to 20 female mice were vaccinated with one of the vaccines or a placebo, and some animals received a second dose of the same vaccine or placebo a month later.

Three weeks later, the researchers measured antibody levels in the mice’s blood as a measure of the strength of their immune response.

Both vaccines elicited very high levels of neutralizing antibodies against Zika, while the placebos did not.

After the mice became pregnant, they were infected with Zika on the sixth day of pregnancy, to mimic the experience of a woman bitten by a Zika-carrying mosquito early in pregnancy.

One week after infection, the researchers measured the amount of virus in the mothers and fetuses.

With both vaccines, fetuses and placentas from vaccinated mice contained very low levels of Zika’s genetic material.

For the mRNA vaccine, more than half of the placentas and fetuses had no detectable viral genetic material at all.

The live-attenuated vaccine was even more effective. In 78% of the placentas and 83% of the fetuses, no viral genetic material was found.

“The amount of viral genetic material in the placentas and fetuses from the vaccinated females was just above the limit of detection,” Dr Diamond said. “It’s not totally clear whether it was infectious virus or just remnants of viruses that had already been killed.”

In contrast, the amount of detectable viral material in the placentas and fetuses of unvaccinated mice was hundreds to thousands of times higher.

The researchers repeated the experiment with different mice so they could evaluate the pups at birth.

None of the mothers in the placebo group made it to term. The mothers became seriously ill, many of the fetuses showed high levels of infection and died in utero, and the placentas showed severe damage.

In contrast, the vaccinated mothers remained healthy, all of their pups were born without obvious signs of injury, and the newborn pups had no measurable Zika virus in their heads.

“In general, most doctors don’t want to vaccinate during pregnancy on the outside chance that the immune response itself could harm the fetus,” Dr Diamond said. “But if you’re in an area where Zika is circulating, you might vaccinate during pregnancy because the risk of Zika infection is worse than some theoretical risk of immune-mediated damage.”

The researchers did not assess whether the vaccines are safe and effective for use during pregnancy.

Such studies couldn’t really be done in mice, Dr Diamond explained, because mouse pregnancies only last 19 days. That doesn’t allow enough time for a protective immune response to develop before the pups are born.

Additionally, this study did not address the question of whether the vaccines work when pregnant women are infected with Zika through sexual contact. It is possible that Zika virus in semen can travel to the uterus and then to the fetus without passing through the bloodstream.

“The question is, ‘Would the immunity still hold up if the virus does not pass through the bloodstream?’“ Dr Diamond said. “We think it will hold up, but that has to be tested.”

Goldsmith/CDC

Researchers have reported that 2 different vaccines can protect mice from Zika virus-induced congenital disease.

Female mice that were vaccinated before pregnancy and infected with Zika virus while pregnant bore pups that showed no trace of the virus.

These results, published in Cell, offer the first evidence that a vaccine administered prior to pregnancy can protect fetuses from Zika infection and resulting injury.

“There are several vaccines in human trials right now, but, to date, none of them has been shown to protect during pregnancy,” said Michael S. Diamond, MD, PhD, of Washington University School of Medicine in St. Louis, Missouri.

“We tested 2 different vaccines, and they both provided substantial protection.”

Last year, Dr Diamond and his colleagues developed a mouse model of Zika infection that mimics the effects of the infection in pregnant women.

Using this model, the researchers evaluated the ability of 2 vaccines to protect fetuses whose mothers were infected during pregnancy.

One of the vaccines is a messenger RNA (mRNA) vaccine, developed by Moderna Therapeutics, that is currently in safety testing in men and women who are not pregnant.

The other is a live-attenuated vaccine, developed by the University of Texas Medical Branch, that is being tested in animals.

For this study, groups of 18 to 20 female mice were vaccinated with one of the vaccines or a placebo, and some animals received a second dose of the same vaccine or placebo a month later.

Three weeks later, the researchers measured antibody levels in the mice’s blood as a measure of the strength of their immune response.

Both vaccines elicited very high levels of neutralizing antibodies against Zika, while the placebos did not.

After the mice became pregnant, they were infected with Zika on the sixth day of pregnancy, to mimic the experience of a woman bitten by a Zika-carrying mosquito early in pregnancy.

One week after infection, the researchers measured the amount of virus in the mothers and fetuses.

With both vaccines, fetuses and placentas from vaccinated mice contained very low levels of Zika’s genetic material.

For the mRNA vaccine, more than half of the placentas and fetuses had no detectable viral genetic material at all.

The live-attenuated vaccine was even more effective. In 78% of the placentas and 83% of the fetuses, no viral genetic material was found.

“The amount of viral genetic material in the placentas and fetuses from the vaccinated females was just above the limit of detection,” Dr Diamond said. “It’s not totally clear whether it was infectious virus or just remnants of viruses that had already been killed.”

In contrast, the amount of detectable viral material in the placentas and fetuses of unvaccinated mice was hundreds to thousands of times higher.

The researchers repeated the experiment with different mice so they could evaluate the pups at birth.

None of the mothers in the placebo group made it to term. The mothers became seriously ill, many of the fetuses showed high levels of infection and died in utero, and the placentas showed severe damage.

In contrast, the vaccinated mothers remained healthy, all of their pups were born without obvious signs of injury, and the newborn pups had no measurable Zika virus in their heads.

“In general, most doctors don’t want to vaccinate during pregnancy on the outside chance that the immune response itself could harm the fetus,” Dr Diamond said. “But if you’re in an area where Zika is circulating, you might vaccinate during pregnancy because the risk of Zika infection is worse than some theoretical risk of immune-mediated damage.”

The researchers did not assess whether the vaccines are safe and effective for use during pregnancy.

Such studies couldn’t really be done in mice, Dr Diamond explained, because mouse pregnancies only last 19 days. That doesn’t allow enough time for a protective immune response to develop before the pups are born.

Additionally, this study did not address the question of whether the vaccines work when pregnant women are infected with Zika through sexual contact. It is possible that Zika virus in semen can travel to the uterus and then to the fetus without passing through the bloodstream.

“The question is, ‘Would the immunity still hold up if the virus does not pass through the bloodstream?’“ Dr Diamond said. “We think it will hold up, but that has to be tested.”