BioEd Online

Researchers have found one small part of a baby's immune system that seems to be all grown up. They say that tickling this adult-like molecule might help to bump up the effectiveness of infant vaccines.

Newborns have immature immune systems that don't respond very well to jabs. Most inoculations are therefore given from around two months of age, when the system is mature enough to react to a vaccine. Even then a child will often get repeated booster jabs.

Now Ofer Levy at Children's Hospital Boston, Massachusetts, and his colleagues have pinpointed one element of the newborn immune system that might be called upon to help a baby's body respond more effectively to a jab. To find a portion that behaves in such an adult fashion is "remarkable" says Levy.

Spot the similarity

Many scientists are working to pinpoint genes and proteins that underlie the differences between babies' and adults' immune systems.

Levy focused on a key family of ten molecules called toll-like receptors (TLRs). These perch on the outside of certain types of white blood cells, where they recognize invading viruses and bacteria and provoke an immune response. The researchers examined receptors on blood cells tapped from babies' umbilical cords at birth, to get an idea of how infant TLRs work.

A few years ago, Levy's team had found that nine of the ten TLRs in a baby's blood do not respond to bacterial proteins in the same way as adult TLRs¹. One, called TLR-8, seemed to be different.

Now they have found that when TLR-8 is stimulated with viral genetic material or chemicals, it triggers particular immune cells called antigen-presenting cells to react just as the adult versions do, releasing certain inflammatory molecules called cytokines². These cells are central to the body's response to vaccines.

Levy believes that a compound that stimulates TLR-8 could be used as an adjuvant, which is given alongside a vaccine and fuels the body's response. Levy says that he next wants to try out this idea in newborn monkeys.

Wide awake

"Boosting vaccine efficacy for children is an important issue," agrees Richard Lo-Man, who studies neonatal immunology at the Institut Pasteur in Paris, France.

Many scientists are already working on ways to awaken the immune system by stimulating TLRs, either in order to boost vaccine responses or to combat cancer. Some compounds are already being tested in clinical trials.

If such an approach worked, it could allow babies to be vaccinated at birth and avoid the perilous period when they are defenceless against pathogens. It could also help to ensure that more babies receive jabs, because it could be done in a single visit when the mother is visiting a medical worker for the birth. In developing countries, it can be difficult for new mothers to return to a clinic for follow-up visits after giving birth.

Risky business

Levy and Lo-Man acknowledge that the idea of manipulating a newborn's immune system should be approached with great caution, because of the risk of side effects. Nobody knows, for example, whether a newborn can withstand adult levels of cytokines. "The benefit/risk issue is a major concern," Lo-Man says.

But Levy points out that it has precedent: the hepatitis B vaccine is already given immediately after birth because, for unknown reasons, it shows some effectiveness at this stage.

Because the public health benefits could be so great, "I don't think we can sit back and not even try," he says.

Visit our newsblog to read and post comments about this story.