Friday, May 17 2013 11:17 PM EDT2013-05-18 03:17:33 GMT
An inmate is on the loose in Etowah County. The Sheriff's department says an inmate kitchen worker escaped the Etowah County Detention Center (ECDC) Friday morning. Justin Wade Hopkins, 30, escaped fromMore >>
The Etowah County Sheriff's Office says an inmate kitchen worker escaped the Etowah County Detention Center Friday morning. More >>
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SOURCE Boston Children's Hospital
Promising compound may help protect babies during vulnerable window
BOSTON, March 4, 2013 /PRNewswire-USNewswire/ -- 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 global health. 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 health care provider.
While newborns lack most aspects of the immune response, 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 PLoS ONE, 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 human immune system 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 white blood cells 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."
The current study was supported by VentiRx Pharmaceuticals and grants from the National Institutes of Health (R01 18AI100135-01). Dowling and Zhen Tan, MD of the Division of Infectious Diseases at Boston Children's Hospital share first authorship on the paper. Coauthors were Zofia Prokopowicz, PhD, and Christine Palmer, PhD, of Boston Children's, and Maura-Ann Matthews, PhD, Gregory Dietsch, PhD, DABT, and Robert Hershberg, MD, PhD, of VentiRx.
For further background on the Levy lab's work, see this blog post.
Boston Children's Hospitalis home to the world's largest research enterprise based at a pediatric medical center, where its discoveries have benefited both children and adults since 1869. More than 1,100 scientists, including nine members of the National Academy of Sciences, 11 members of the Institute of Medicine and 11 members of the Howard Hughes Medical Institute comprise Boston Children's research community. Founded as a 20-bed hospital for children, Boston Children's today is a 395-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families. Boston Children's also is a teaching affiliate of Harvard Medical School. For more information about research and clinical innovation at Boston Children's, visit: http://vectorblog.org/.
Saturday, May 18 2013 8:53 PM EDT2013-05-19 00:53:15 GMT
One person is dead Saturday after a police chase ended with a head-on collision in Tuscaloosa.According to the Tuscaloosa Police Department, the male suspect fleeing from officers died in the two-vehicleMore >>
One person is dead Saturday after a police chase ended with a head-on collision in Tuscaloosa.More >>
Saturday, May 18 2013 8:33 PM EDT2013-05-19 00:33:05 GMT
By JOHN ZENORAP Sports Writer BIRMINGHAM, Ala. (AP) - Nick Saban's scowling face now greets fans coming into the state of Alabama Sports Hall of Fame and a box of his cherished oatmeal cream pies restsMore >>
Nick Saban's scowling face now greets fans coming into the state of Alabama Sports Hall of Fame and a box of his cherished oatmeal cream pies rests at his feet.More >>
Saturday, May 18 2013 7:25 PM EDT2013-05-18 23:25:44 GMT
The National Weather Service in Birmingham has issued a flood warning in Jefferson and Shelby Counties until late Sunday night due to rising waters in the Cahaba River.The upper Cahaba River drainage basinMore >>
The National Weather Service in Birmingham has issued a flood warning in Jefferson and Shelby Counties until late Sunday night due to rising waters in the Cahaba River.More >>
Saturday, May 18 2013 6:43 PM EDT2013-05-18 22:43:37 GMT
Escambia County Sheriff's deputies are searching for a missing 7-year-old autistic boy who was last seen Friday afternoon on Perdido Key Drive in the vicinity of the Needle Rush condos. Owen Black wasMore >>
Escambia County Sheriff's deputies are searching for a missing 7-year-old autistic boy who was last seen Friday afternoon on Perdido Key Drive in the vicinity of the Needle Rush condos.More >>
Saturday, May 18 2013 6:33 PM EDT2013-05-18 22:33:41 GMT
The Hatton High School softball team won its fourth straight Class 2A state title Friday while Haleyville captured its second straight title in Class 4A. The Sparkman girls capped off an undefeated seasonMore >>
Haleyville captured its second straight title in Class 4A while the Sparkman girls capped off an undefeated season by winning the Class 6A crown in the AHSAA state softball championships at Lagoon Park in Montgomery.More >>
Saturday, May 18 2013 6:17 PM EDT2013-05-18 22:17:05 GMT
The Hartselle High School baseball team staged an exciting comeback in the final two innings to overcome Spanish Fort and win the Class 5A state baseball championship Saturday at Montgomery's RiverwalkMore >>
Hartselle staged an exciting comeback in the final two innings to overcome Spanish Fort and win the Class 5A state baseball championship Saturday in Montgomery. More >>
Saturday, May 18 2013 6:06 PM EDT2013-05-18 22:06:23 GMT
TUSCALOOSA, Ala. -- In a back-and-forth affair the Alabama softball team held off Western Kentucky, 7-6, Saturday afternoon in day two of the NCAA Softball Tuscaloosa Regional at Rhoads Stadium. WithMore >>
In a back-and-forth affair the Alabama softball team held off Western Kentucky, 7-6, Saturday afternoon in day two of the NCAA Softball Tuscaloosa Regional.More >>
Saturday, May 18 2013 4:22 PM EDT2013-05-18 20:22:26 GMT
According to Alabama Power, heavy and unexpected rains have tipped water levels at Logan Martin and Harris lakes over its normal summer pools and are affecting spillway operations. Lake Reports: LoganMore >>
According to Alabama Power, heavy and unexpected rains have tipped water levels at Logan Martin and Harris lakes over its normal summer pools and are affecting spillway operations.More >>