July 31, 2000 -- For the first time, scientists have induced immunity to a virus in newborns by vaccinating them while they were still in their mothers' wombs. If these animal findings hold up in humans, the researchers tell WebMD, they could help eliminate the transmission from mother to infant of such devastating diseases as herpes, hepatitis, and AIDS.
Today "if a mother has HIV, the fetus is almost guaranteed to contract the disease through vaginal fluids during birth or later through breast milk," says researcher Philip J. Griebel, DVM, PhD. In the Western world, the transmission rate has been lowered by performing cesarean sections on HIV-positive women and instructing them not to breastfeed, but "that's not 100% effective." And tragically, he says, less-developed countries now face "the loss of an entire generation" to the rampant spread of AIDS. Vaccinations in the womb could be a potential way of breaking the cycle of transmission, he tells WebMD.
Griebel heads the immunology department in the veterinary infectious disease organization at University of Saskatchewan in Canada. His team's findings appear in the journal Nature Medicine.
Previously, Griebel says, many researchers believed that "the fetus cannot produce an immune response [to fight infections]. But we've disproved that." With "a simple vaccine that requires no complicated formulation and no dangerous, foreign compounds, we have induced a complete immune response, similar to what we'd see in mature animals [who are exposed to a virus]."
Griebel's team injected the DNA of a herpes virus that infects cows into the mouths of four fetal lambs. Another four animals received an inert vaccination as a control. Tests on the fetuses showed no negative effects from the vaccination. The mother ewes remained healthy, and all eight lambs were completely normal at birth.
Although similar experiments have been attempted in baboons, "the novelty here is that they used a DNA[-based] vaccination," says Michael Lai, MD, PhD, a professor of molecular microbiology and immunology at University of Southern California School of Medicine in Los Angeles, who reviewed the research for WebMD.
Not only is this type of vaccine easier to mass-produce, Griebel says, but it is much safer than vaccines made with live or weakened viruses.
After giving the vaccinations, the researchers performed an extensive series of tests to prove that the fetal lambs had developed immunity to the herpes virus. The blood of all four vaccinated fetuses did indeed carry antibodies to the virus -- even more antibodies than were found in the blood of newborn lambs vaccinated two or three days after birth. None of the fetal lambs injected with the placebo vaccine carried these antibodies.
This is especially important, Griebel says, because when a baby is vaccinated, it can take 7-10 days for immunity to develop, "by which time transmission will have occurred. That's why we're stepping back and doing the vaccination in utero."
Even more critical than circulating antibodies, Griebel tells WebMD, was showing that immune cells in the mucous membranes, such as the mouth and lungs and intestines, could fight off the virus. "Mucosal immunity is most important," he explains, because those are the body surfaces where pathogens actually enter -- the mouth, the lungs, the intestines.
While the findings are "remarkable" and promising, he tells WebMD, much more work is needed. These experiments showed that the fetal immune system could recognize and fight off the herpes virus in a test tube, but the lambs themselves weren't ever exposed to the disease, he says.
But the team has already taken the next step. They successfully replicated this work, then vaccinated these newborn lambs with a second dose. "We showed that immunity was strengthened" by a booster shot, without any side effects, he says.
Because human beings are much more genetically diverse than laboratory animals, vaccinations provide different people with different levels of protection, Griebel says. "Even our best vaccinations only provide full immunity about 70% of the time," he says, "but boosters can bring that percentage up closer to 100."
Next, Griebel's team will repeat the lamb experiment using a virus that more closely resembles HIV. They will also expose the newborn animals to the virus. If successful, they'll move on to primates.
Griebel emphasizes that the ultimate goal of the work is eliminating the spread of HIV from mother to child. Although this technology is relatively safe, fetal procedures of any kind are not without risk, he says. That's why "we're proposing this [only for use against] diseases that have very high risk of transmission during and immediately after birth."
According to Lai, who is also a researcher at Howard Hughes Medical Institute in Chevy Chase, Md., "the findings clearly show that a fetus can develop immunity. This approach would be useful in hepatitis B, and in respiratory viruses that cause infection right after delivery. Inducing immunity before birth would certainly be very useful."
But to be applicable in the real world, Griebel says, "we need a good vaccine candidate" for HIV. In other words, he explains, "we've shown that [the delivery] ... method works -- at least in lambs." What is still needed, and what "people all over the world are working on," is a vaccine to deliver.