'Holy grail' for boosting infant immunity

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http://www.washingtontimes.com/upi/20060425-042954-4402r.htm

'Holy grail' for boosting infant immunity

By Dell'Amore

UPI Consumer Health Correspondent

Apr. 25, 2006

Researchers have identified a way to stimulate the immune systems of

newborns, possibly boosting the effectiveness of early vaccines

against common, life-threatening infections.

Babies are born with weak immune systems, which puts them at a

higher susceptibility to both bacterial and viral infection that can

lead to severe complications, including death. As a result, vaccines

that could prevent against infection tend to be ineffective in

newborns. But by triggering one of the body's proteins -- called a

toll-like receptor, or TLR -- a newborn's immune system could react

and defend the body against foreign invaders.

" We've stumbled across a molecular holy grail in newborn

immunology, " said lead author Dr. Ofer Levy, a principal investigator

of the Division of Infectious Diseases at Children's Hospital in

Boston.

The paper was published April 25 in the online edition of the

journal Blood. One of the authors on the paper was a 3M

representative, which sells medical equipment and technology.

Levy and colleagues collected blood from healthy adults, as

well as newborn cord blood, to conduct laboratory tests. The

researchers focused their study on the 10 TLRs that exist in the

body. In adults, TLRs work together as the body's key defense against

infection, mobilizing the white blood cells.

But in newborns, TLRs aren't activated. Part of the reason is

evolutionary: if the fetus were to send out inflammatory immune

responses, the mother's body might reject it. Evolution has skewed

the newborn's immune system to avoid these immune responses.

But the research team discovered they could actually spur one

of the TLRs to protect against invaders -- TLR8. Using harmless

agents that mimic viral antigens, the researchers were able to elicit

a robust reaction from TLR8's white blood cells. This reaction could

potentially help vaccines work more efficiently in newborns.

Since TLRs were only discovered in the last decade or so,

Levy's research on infants builds on a new story in biology, he said.

Children could be vaccinated earlier against dangerous

infections like respiratory syncytial virus (RSV), a flu-like virus;

pneumococcus; HIV, and rotavirus.

" If we could develop a vaccine to give at birth, we could close

the window of vulnerability in the very young, " Levy said.

Most vaccines are given at two, four and six months, which

leaves the child susceptible, he added.

An adjuvant -- or add-on -- containing the TLR8-stimluating

agent could be given in conjunction with a vaccine at birth, which

would ultimately strengthen the newborn's resistance to disease.

The research also has a global impact, Levy said. In many

developing countries in Africa, for instance, newborns only visit

healthcare providers at birth. From a practical standpoint, a vaccine

given at birth could translate to better health coverage in countries

where regular visits to the doctor are few and far between.

Based on the dramatic immune effects in the lab, Levy plans to

start testing on animal models.

The research has the potential as a breakthrough for treating

infections in newborns, said on, professor of

pediatrics in pediatric infectious diseases at Children's Mercy

Hospital in Kansas City.

" It's exciting because it is a tool that can be harnessed to

bring a part of the immune system up to the point where it might

process antigens like a 2- or 3-month-old, " he said.

The only protection babies have when they are born are

antibodies from the mother's placenta while in utero. on and

other researchers have been trying to find ways to get the babies

ready to be out in the cold cruel world where they can be attacked by

various infections, he said.

Children born in unsterile conditions or whose mothers have HIV

would be ideal candidates for early vaccines, said Cashore, a

professor of pediatrics at Brown University. An HIV vaccine has not

yet been developed.

Cashore said Levy's research on TLR8 is opening new doors to

understanding newborn immunity.

" It's a bit like having a skeleton key -- a tool which allows

you to take a first step that's otherwise not available, " he said.