Dartmouth researchers find that maternal antibodies against HSV-1 can protect their infants from the virus
Geisel School of Medicine at Dartmouth News Jul 21, 2017
While modern medicine has produced a number of excellent anti–viral drugs to treat herpes simplex virus, none have been able to eliminate its latency. ÂConsequently, there is this constant reservoir of virus in the community, just waiting to reactivate and spread to new, susceptible individuals, said David Leib, PhD, a professor of microbiology and immunology at DartmouthÂs Geisel School of Medicine.
Most at risk are newborn infants, who are highly susceptible to infection due to their immature immune systems and can contract the virus from their infected mothers as they pass through the birth canal.
ÂIn newborns this can be severe, causing brain damage or death – recent epidemiological studies are starting to recognize the significant global burden of such neonatal HSV infections, explained Leib.
However, findings from a study publishedin the journal mBio®, headed by Leib and his research team at Geisel, are shedding new light on the important role that maternal antibodies can play in protecting neonatal nervous systems against infections.
In a series of laboratory experiments utilizing mouse tissue, as well as human tissue, the investigators found that antibodies produced by adult women or female mice were able to migrate easily to the nervous systems of their unborn babies. They were then able to show that these maternal antibodies fully protected newborn mice from acquiring HSV–1.
ÂWhat this tells us is that women who get pregnant who have a pre–existing herpes infection have a mature immune response to that virus and will pass those antibodies to their baby, Leib says. ÂIf that baby should be infected during delivery, it will be protected because the motherÂs antibodies get into its nervous system before birth. But, if women acquire the virus during pregnancy, the risk of severe outcomes for the newborn can be significant, as high as 50 percent.Â
ÂMaternal antibodies providing protection to infants nervous systems hasnÂt been noted before, and is very important for pathogens that infect newborns because there is often some kind of neurologic consequence that may impact their entire lives, says Yike Jiang, an MD–PhD student at Geisel who served as lead author on the study. Other collaborators included Andrew Pachner, MD, and Francesca Gilli, PhD, from neurology and Lananh Nguyen, MD, MS, from pathology.
Remarkably, it was Âtotal serendipity that led to the studyÂs initial observation, made by Jiang. ÂIt was something that she discovered because a series of control experiments she was doing, looking for something else – a certain type of cell in the nervous system – kept coming up positive, says Leib, whoÂs laboratory focuses primarily on examining viral pathogenesis at the molecular level.
ÂI think it was YikeÂs unique perspective, drawn from her dual training as a clinician–scientist and from the fact that sheÂs just a terrific student, that really drove this project, he says. ÂShe recognized the significance of the data she was getting before anyone else. It then became sort of a hot topic once we knew what we were on to.Â
Next, Leib and his colleagues plan to test the efficacy of existing HSV–1 vaccines in their mouse neonatal model. These vaccines have been developed to stop adult–to–adult or Âhorizontal transmission of the virus, and none have succeeded in clinical trials.
ÂWhat weÂre proposing is the idea that they should be reinvestigated to look at so–called Âvertical protection – that is, protection thatÂs passed from the mother to the fetus or newborn, he says. ÂMaternal immunization, either through administering a vaccine or introducing antibodies, may also be an effective strategy to use against other pathogens that affect newborns, like the Zika virus.Â
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Most at risk are newborn infants, who are highly susceptible to infection due to their immature immune systems and can contract the virus from their infected mothers as they pass through the birth canal.
ÂIn newborns this can be severe, causing brain damage or death – recent epidemiological studies are starting to recognize the significant global burden of such neonatal HSV infections, explained Leib.
However, findings from a study publishedin the journal mBio®, headed by Leib and his research team at Geisel, are shedding new light on the important role that maternal antibodies can play in protecting neonatal nervous systems against infections.
In a series of laboratory experiments utilizing mouse tissue, as well as human tissue, the investigators found that antibodies produced by adult women or female mice were able to migrate easily to the nervous systems of their unborn babies. They were then able to show that these maternal antibodies fully protected newborn mice from acquiring HSV–1.
ÂWhat this tells us is that women who get pregnant who have a pre–existing herpes infection have a mature immune response to that virus and will pass those antibodies to their baby, Leib says. ÂIf that baby should be infected during delivery, it will be protected because the motherÂs antibodies get into its nervous system before birth. But, if women acquire the virus during pregnancy, the risk of severe outcomes for the newborn can be significant, as high as 50 percent.Â
ÂMaternal antibodies providing protection to infants nervous systems hasnÂt been noted before, and is very important for pathogens that infect newborns because there is often some kind of neurologic consequence that may impact their entire lives, says Yike Jiang, an MD–PhD student at Geisel who served as lead author on the study. Other collaborators included Andrew Pachner, MD, and Francesca Gilli, PhD, from neurology and Lananh Nguyen, MD, MS, from pathology.
Remarkably, it was Âtotal serendipity that led to the studyÂs initial observation, made by Jiang. ÂIt was something that she discovered because a series of control experiments she was doing, looking for something else – a certain type of cell in the nervous system – kept coming up positive, says Leib, whoÂs laboratory focuses primarily on examining viral pathogenesis at the molecular level.
ÂI think it was YikeÂs unique perspective, drawn from her dual training as a clinician–scientist and from the fact that sheÂs just a terrific student, that really drove this project, he says. ÂShe recognized the significance of the data she was getting before anyone else. It then became sort of a hot topic once we knew what we were on to.Â
Next, Leib and his colleagues plan to test the efficacy of existing HSV–1 vaccines in their mouse neonatal model. These vaccines have been developed to stop adult–to–adult or Âhorizontal transmission of the virus, and none have succeeded in clinical trials.
ÂWhat weÂre proposing is the idea that they should be reinvestigated to look at so–called Âvertical protection – that is, protection thatÂs passed from the mother to the fetus or newborn, he says. ÂMaternal immunization, either through administering a vaccine or introducing antibodies, may also be an effective strategy to use against other pathogens that affect newborns, like the Zika virus.Â
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