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:6/26/2016)...  VMS Rehab Systems, Inc. ( www.vmsrehabsystemsinc.com ) reported ... required to build a strong and stable market for ... on the OTC Markets-pink current trading platform. ... are seeing an anomaly in market trading activities that ... the Company, but shareholders and market players as well. ...
(Date:6/24/2016)... 24, 2016  Collagen Matrix, Inc., ("Collagen Matrix") ... manufacturing of collagen and mineral based medical devices ... Bill Messer has joined the company ... leverage the growing portfolio of oral surgery, neurosurgery, ... Bill joins the Collagen Matrix executive team as ...
(Date:6/24/2016)... DUBLIN , June 24, 2016 ... and Markets has announced the addition of the ... their offering. ... products and provides an updated review, including its applications ... covering the total market, which includes three main industries: ...
Breaking Medicine Technology:
(Date:6/25/2016)... ... ... On Friday, June 10, Van Mitchell, Secretary of the Maryland Department of Health ... of their exemplary accomplishments in worksite health promotion. , The Wellness at Work Awards ... at the BWI Marriott in Linthicum Heights. iHire was one of 42 businesses to ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article ... people are unfamiliar with. The article goes on to state that individuals are now ... of these less common operations such as calf and cheek reduction. The Los Angeles ...
(Date:6/24/2016)... ... ... June 19, 2016 is World Sickle Cell Observance Day. In an effort to ... treatments, Serenity Recovery Center of Marne, Michigan, has issued a pain management ... (SCD) is a disorder of the red blood cells, which can cause episodes of ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension Association ... it will receive two significant new grants to support its work to advance ... 25th anniversary by recognizing patients, medical professionals and scientists for their work in ...
(Date:6/24/2016)... ... June 24, 2016 , ... Dr. Amanda Cheng, an ... Dr. Cheng has extensive experience with all areas of orthodontics, including robotic Suresmile ... orthodontics. , Micro-osteoperforation is a revolutionary adjunct to orthodontic treatment. It can ...
Breaking Medicine News(10 mins):