DNA vaccine immunizes fetal lambs

Although a woman’s placenta shields her fetus from most infections she carries during pregnancy, microbes sometimes pounce on a baby during or shortly after birth. In this way, many mothers inadvertently transmit diseases such as herpes simplex to their child.

In the August Nature Medicine, scientists report successfully vaccinating fetal lambs against bovine herpes, to which sheep are susceptible. The study bolsters a nascent technology that aims to protect human infants still in the womb from diseases of their mothers.

The researchers squirted a DNA vaccine into the mouths of fetal lambs using a needle inserted through an incision in the mother sheep. The scientists delivered the vaccine on day 124 of the sheep’s 148-day gestation period. A few weeks later, after the ewes gave birth vaginally, tests showed the technique had immunized all 12 fetal lambs given the vaccine but had no effect on the mothers, says study coauthor Lorne A. Babiuk, a virologist at the University of Saskatchewan in Saskatoon. The lambs received an oral booster dose after birth.

The initial vaccination had induced moderate antibody buildup against bovine herpes, says Babiuk. The booster hiked this immunity dramatically—apparently to a protective level. The researchers currently are exposing the lambs to bovine herpes virus to determine whether they are indeed immune.

The DNA vaccine contains a herpes-virus gene. Specialized immune cells accept this gene and display on their sufaces the glycoprotein it encodes. The body then recognizes the glycoprotein as foreign and launches an immune response.

The vaccinations “worked a lot better than we had expected,” Babiuk says. For example, antibodies against the herpes virus appeared in the newborn lambs’ neck lymph glands as well as in their blood, he says. This suggests significant mucosal immunity—so named because it fends off microbes that latch onto the mucus-lined surfaces of the mouth and throat. Mucosal protection is important for newborns because during birth they come into contact with—and often ingest—viruses or bacteria in their mother’s blood or other fluids.

In addition, concentrations of the hormone cortisol in the lambs at birth matched those seen in newborn lambs getting an inert vaccine. Babiuk and his colleagues consider this a sign of normal development.

The study hints that fetal mammals can rally an immune response if properly stimulated, Babiuk says. Herpes simplex, hepatitis B, and group B streptococcus can all be passed on at birth, making them candidates for fetal vaccination, he says.

The research represents “a very interesting development,” says Stephen A. Johnston of the University of Texas, Southwestern Medical Center in Dallas. The vaccine-delivery technique used in the study may not be practical for widespread use, but it likely will spawn more research into in utero vaccination, he says.

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