A vaccine that works in newborns? Promising compound may help protect babies during vulnerable window

March 4, 2013, Children's Hospital Boston

The underdeveloped immune systems of newborns don't respond to most vaccines, leaving them at high risk for infections like rotavirus, pertussis (whooping cough) and pneumococcus. Researchers at Boston Children's Hospital have identified a potent compound that activates immune responses in newborns' white blood cells substantially better than anything previously tested, and that could potentially make vaccines effective right at birth.

The ability to immunize babies at birth—rather than two months of age, when most current vaccination series begin—would be a triumph for . Worldwide, each year, infections kill more than 2 million infants under 6 months old. In resource-poor countries, birth may be the only time a child has contact with a .

While lack most aspects of the , researchers led by Ofer Levy, MD, PhD, of the Division of Infectious Disease at Boston Children's have shown that their white blood cells do have one receptor that responds strongly to stimulation, known as Toll-like receptor 8 (TLR 8). In their new work, published March 4 by the online open-access journal , they tested a panel of synthetic small-molecule compounds that specifically target TLR8, known chemically as benzazepines.

The compounds, provided by VentiRx Pharmaceuticals (Seattle, WA), potently stimulate the and are in clinical trials in patients with certain cancers.

Tested in Levy's lab, one benzazepine, VTX-294, produced a strong immune response in from newborns (taken from cord blood samples) as well as whole blood from adults. It induced robust production of cytokines—chemicals that rally the immune response—and proved at least 10 times more potent than the best activator of TLR8 known previously.

"The response was not only equal to that in adults, but VTX 294 was sometimes actually more effective in newborns than adults," notes Levy, the study's senior investigator.

The compound also triggered production of so-called co-stimulatory molecules that enhance immune responses. Moreover, even very low concentrations of VTX-294 strongly activated antigen-presenting cells, a type of white blood cell whose activation induces immune memory—key to effective responses to vaccines.

Toll-like receptors (TLRs), first identified in humans about two decades ago, are part of the innate (rapid) immune response that provides our first defense against infections. Ten types of TLRs are known, and TLR stimulators have begun to be added to vaccines as adjuvants. The main one, monophosphoryl lipid A (MPLA), stimulates TLR4 and is used in the human papillomavirus vaccine Cervarix. However, in a recent clinical trial published in The New England Journal of Medicine, a malaria vaccine with MPLA failed to elicit a sufficient immune response in infants.

With encouraging results in cells from human newborns, Levy and colleagues now hope to formulate VTX 294 or a similar TLR8 stimulator for testing as a vaccine adjuvant in newborn primates, a model in which the lab has expertise, and whose responses to TLR8 closely resemble humans'.

"This one receptor seems to lead to more adult-like responses—immediate, short-term responses that are more appropriate for fighting infections," says David Dowling, PhD, co-first author on the study. "We're excited about the benzazepines because they are already in the clinical pipeline. That advances the potential for using them in a clinical study in human newborns, once they have been proven safe in animal studies."

Explore further: An advance for a newborn vaccine approach

Related Stories

An advance for a newborn vaccine approach

April 13, 2011
(PhysOrg.com) -- Infectious disease is a huge cause of death globally, and is a particular threat to newborns whose immune systems respond poorly to most vaccines. A new approach developed at Children's Hospital Boston, using ...

Modeling sepsis in newborns

September 6, 2012
Sepsis, or bacterial infection of the bloodstream, is a grave, hard-to-diagnose threat in premature newborns in the NICU. Even when it's detected and treated with antibiotics, its inflammatory effects can harm fragile babies' ...

Research describes advantages of new vaccine adjuvant

December 12, 2011
New research from the laboratory of Dr. Elizabeth Leadbetter at the Trudeau Institute may lead to a whole new class of vaccines. Dr. Leadbetter's lab has discovered new properties of a potential vaccine adjuvant that suggest ...

Recommended for you

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

How the immune system's key organ regenerates itself

January 15, 2018
With advances in cancer immunotherapy splashing across headlines, the immune system's powerful cancer assassins—T cells—have become dinner-table conversation. But hiding in plain sight behind that "T" is the organ from ...

Immunosuppressive cells in newborns play important role in controlling inflammation in early life

January 15, 2018
New research led by The Wistar Institute, in collaboration with Sun Yat-sen University in China, has characterized the transitory presence of myeloid-derived suppressor cells (MDSCs) in mouse and human newborns, revealing ...

Memory loss from West Nile virus may be preventable

January 15, 2018
More than 10,000 people in the United States are living with memory loss and other persistent neurological problems that occur after West Nile virus infects the brain.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.