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Vaccine Adjuvant May Boost Babies' Immune Response

Babies may soon be able to receive vaccinations against a wider range of pathogens, according to a new study. In vitro research into a novel adjuvant has shown promise in bringing forward the age at which a baby may safely be vaccinated – a possibility with enormous public health implications.

The study was published in Blood in an advance online publication and reported by MedPage Today on April 25, 2006.

At birth, babies do not have fully developed immune systems and cannot respond adequately to most vaccines, which makes them vulnerable to infection, according to Ofer Levy, MD, PhD, of Children’s Hospital in Boston.

"The medical issue is that you have a window of vulnerability during the first weeks and months of life," Dr Levy said in an interview.

Dr Levy and colleagues’ studies report on an adjuvant approach to vaccination that seems to boost the neonatal immune response to adult levels.

"The effect that we show in the test tube is very dramatic," Dr Levy said. "We get a response that’s equivalent to an adult response, and that’s remarkable."

Neonatal Immune System

Newborns’ immune systems are believed to be too immature to respond properly to an antigen. For this reason, babies are usually immunized starting at a few months of age.

Babies’ immune systems are biased towards a T-helper cell type II (TH2) response, according to Dr Levy. This response is believed to protect babies’ against inflammatory responses whose consequence may include premature delivery.

Because the TH2 response is favored, the TH1 response – which protects against infection – is less effective, Dr Levy said.

The TH1 response involves a chain of biochemical and physiologic reactions that begins with stimulation of cell receptors called “Toll-like receptors” on antigen-presenting cells (APCs).

"We found that when most Toll-like receptors (TLRs) are stimulated, newborns’ immune responses are very impaired," Dr Levy said. "But there was one important exception."

This exception occurs with TLR8-stimulation of APCs, which produces normal adult levels of proteins associated with the immune response.

"[TLR]Eight is enough," he said. "For other Tolls, the baby response was muted."

Dr Levy and colleagues hypothesize that coupling a TLR8 agonist with a vaccine, such as for respiratory syncytial virus or pertussis, would provide effective early protection against these diseases.

However, the researchers cautioned that results to date are limited to in vitro analysis and require further investigation before the approach may be tested in humans. Animal studies are now being organized.

Advantages of such a vaccine would be particularly felt in the Third World, according to Dr Levy, where "birth is often the only contact a child will have with the health-care system." He added that a vaccination program targeting newborns would potentially greatly reduce mortality and morbidity in such countries.

Vaccine Adjuvant May Boost Babies' Immune Response, MedPage Today, April 25, 2006.
Unique efficacy of Toll-like receptor 8 agonists in activating human neonatal antigen-presenting cells. Ofer Levy et al., Blood, pre-published online April 25, 2006.

Posted: April 2006