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:6/24/2016)... and SAN CLEMENTE, Calif. , June 24, 2016 ... mobile pulmonary function testing company, is now able to perform sophisticated ... by ndd Medical Technologies , Inc. Patients ... hospital-based labs.  Thanks to ndd,s EasyOne PRO ® , ARL patients ... get any needed testing done in the comfort of her own ...
(Date:6/24/2016)... , June 24, 2016 VolitionRx ... of Dr. Edward Futcher to the ... effective June 23, 2016.Dr. Futcher was also appointed ... Governance Committees.  As a non-executive member of the ... and strategic counsel to VolitionRx in connection with ...
(Date:6/23/2016)... BEVERLY HILLS, Calif. , June 23, 2016 ... faced the many challenges of the current process. Many of ... option because of the technical difficulties and high laboratory costs ... would have to offer it at such a high cost ... to afford it. Dr. Parsa Zadeh , ...
Breaking Medicine Technology:
(Date:6/27/2016)... ... June 27, 2016 , ... ... today announced its strategic partnership with Connance, a healthcare industry leader providing ... companies’ proven, proprietary technology combine to provide health systems, hospitals and ambulatory ...
(Date:6/27/2016)... ... 27, 2016 , ... TopConsumerReviews.com recently awarded their highest five-star rating to Best ... individuals in the United States and Canada wear eyeglasses. Once considered to be a ... and make a fashion statement. Even celebrities use glasses as a way of creating ...
(Date:6/26/2016)... Creek, Michigan (PRWEB) , ... June 26, 2016 , ... ... joined as sponsor of the 2016 Cereal Festival and World’s Longest Breakfast Table in ... in honor of the city’s history as home to some of the world’s leading ...
(Date:6/26/2016)... ... June 26, 2016 , ... PawPaws brand pet supplements ... that was developed to enhance the health of felines. The formula is all-natural and ... main herbs in the PawPaws Cat Kidney Support Supplement Soft Chews are ...
(Date:6/26/2016)... Lake Orion, Clarkston, Michigan (PRWEB) , ... June ... ... direction with respect to fertility once they have been diagnosed with endometriosis. These ... tolerable intercourse but they also require a comprehensive approach that can help for ...
Breaking Medicine News(10 mins):