Navigation Links
A vaccine that works in newborns?
Date:3/4/2013

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 Hospital is 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/.

CONTACT:
Erin Tornatore
Boston Children's Hospital
617-919-3110 | erin.tornatore@childrens.harvard.edu


'/>"/>
SOURCE Boston Children's Hospital
Copyright©2012 PR Newswire.
All rights reserved

Related medicine technology :

1. Vaccine Manufacturing Technology and Services: World Market 2013-2023
2. New Bioterrorism Vaccine Gets First Test In Humans
3. Cytos VLP Platform is Basis for Phase 1 Clinical Trial with Anti-IgE Vaccine
4. Generex Points to Potential of Antigen Express Technology Platform beyond Its AE37 Breast Cancer Vaccine
5. Targovax AS Announces First Patient Included in Phase I/II Clinical Study With the Therapeutic Cancer Vaccine TG01 in Operable Pancreatic Cancer
6. Research on Chinas Animal Vaccine Industry, 2013-2017
7. Details of HER-2/neu Class I Antigen Licensed by TapImmune published in Journal of Immunology: Antigen is a naturally processed epitope for breast cancer vaccines.
8. Inovios Synthetic Flu Vaccine Doubles Rate of Elderly Subjects Displaying Protective Immune Responses
9. National Institute of Health Awards Contract to Support Use of iBios Proprietary Technology for Improved Anthrax Vaccine
10. OncoSec Medical to Present Data at DNA Vaccines 2012 Conference
11. Axion Health Sponsors Webinar on Vaccine Development Featuring Dengue Fever Case Study
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/24/2017)... 23, 2017  The particle counters market is ... from USD 275.9 million in 2016, at a ... report: http://www.reportlinker.com/p04718602-summary/view-report.html The growing ... R&D, and growth in manufacturing industries in emerging ... for particle counters. On the other hand, technical ...
(Date:2/24/2017)... Feb. 24, 2017  Xynomic Pharmaceuticals, Inc., an oncology ... it has acquired exclusive worldwide rights to develop, ... HDAC inhibitor targeting hematological and solid tumors. ... 1 and 2 clinical trials of Abexinostat in ... have already been completed, demonstrating that Abexinostat is ...
(Date:2/23/2017)... , Feb. 23, 2017 Visiomed, ... and services since 1997, is changing the landscape ... technology providing patients with pro-active, custom-made solutions. Recognizing ... for instant and affordable healthcare without walls, Visiomed ... high-level devices developed with healthcare professionals that is ...
Breaking Medicine Technology:
(Date:2/24/2017)... New York, NY (PRWEB) , ... February 24, 2017 , ... ... urges: “Security needs to be a top priority because it’s not if you will ... in online safety, especially when it comes to digital health care. , Improvements in ...
(Date:2/24/2017)... ... February 24, 2017 , ... With ProGlass Prism users now ... . Users have total control over position, rotation, distortion, edge softness, edge blur, chromatic ... Cut Pro X. , With ProGlass Prism users are given the tools and ...
(Date:2/24/2017)... ... ... Indiana Fiber Network (IFN) President and CEO Kelly C. Dyer recently announced ... the Chairman of the Management Committee when IFN was originally formed in 2002 where ... investor/owners and development of the business plan. He became the first paid employee ...
(Date:2/24/2017)... MI (PRWEB) , ... February 24, 2017 , ... ... in Charlevoix, once again hosted their Military Wedding Giveaway, with the winning ... hosted by Castle Farms with services generously donated from local vendors: A Matter ...
(Date:2/23/2017)... ... February 23, 2017 , ... ... exclusively to funding innovative lymphoma research and serving the lymphoma community through a ... to the La Gorce Country Club in Miami Beach to host its Swirl: ...
Breaking Medicine News(10 mins):