Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New artificial protein mimics a part of the HIV outer coat

23.10.2013
A team of scientists at Duke Medicine and Memorial Sloan-Kettering Cancer Center has created an artificial protein coupled with a sugar molecule that mimics a key site on the outer coat of HIV where antibodies can bind to neutralize a wide variety of HIV strains.

Reported during the week of Oct. 21, 2013, in the journal Proceedings of the National Academy of Sciences, the finding provides a potential new strategy in vaccine development to elicit the broadly neutralizing antibodies considered essential for long-lasting protection from the ever-changing HIV virus.

The new protein was designed by Duke and Harvard University scientists and made by Samuel Danishefsky, Ph.D., and his team at Memorial Sloan Kettering Cancer Center in New York.

"This new protein will allow the testing of a major hypothesis for why broadly neutralizing antibodies are so difficult to produce -- that of competition between desired and undesired antibody responses," said senior author Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute. "By immunizing with a vaccine that primarily has the desired target for the immune system, we will be able to see if the immune system is now free to make this type of response."

Haynes and colleagues built upon a growing body of recent research that has illuminated how the HIV virus manages to thwart potential vaccine candidates, and how the immune system mounts what is ultimately a futile fight.

The targets of protective antibodies are vulnerable regions of the outer coat of the virus, also called the viral envelope. HIV protects these vulnerable envelope regions with multiple strategies that camouflage the sites.

Recent research, however, has demonstrated that the human immune system prefers not to target these vulnerable sites, but instead aims at the outer coat sites that do not result in the production of protective antibodies.

Fostering the preferred broadly neutralizing antibodies has not been a simple matter, because they tend to have unusual features that make them targets for elimination by the body's own immune system. Instead, other, less effective antibodies against HIV dominate and in some instances crowd out the desired broad neutralizing antibodies.

In the most recent study, the researchers found a way to approach those challenges. They built a glyocopeptide - an artificial protein synthesized by organic chemistry with sugars attached - that is structured so that it readily binds to the broadly neutralizing antibodies rather than the more dominant antibodies. That quality is important for allowing the preferred antibodies to have a chance to develop.

The newly synthesized glycopeptide also attaches to the original ancestors of the broadly neutralizing antibodies, with the potential to trigger the receptors on naïve B cells of the neutralizing antibodies. B cells are white blood cells that make antibodies. The researchers believe this feature may be critical for a vaccine to induce antibodies that neutralize the HIV virus.

"It's by presenting the correct target for a neutralizing antibody, yet masking the dominant undesired target, that a vaccine can provide a fair chance for neutralizing antibodies to develop," said lead author S. Munir Alam, Ph.D., professor of medicine and pathology at Duke. "As in the case of our designed glycopeptide, if we start with a vaccine, to which not only the broadly neutralizing antibodies bind well, but also the receptors on naïve B cells, we hope to optimize the chance that the induced antibodies will go down the right path."

Alam said additional studies are ongoing, including efforts to create a crystal structure of the glycopeptide bound to the neutralizing antibody, and to begin testing the glycopeptide in animal models.

In addition to Haynes and Alam, study authors from Duke include S. Moses Dennison, Shelley Stewart, Frederick H. Jaeger, Kara Anasti, Julie H. Blinn, Mattia Bonsigniori, and Hua-Xin Liao. Authors from Sloan-Kettering include Danishefsky, Baptiste Aussedat, Yusuf Vohra, Peter K. Park, and Alberto Fernández-Tejada. Authors from Boston University and Harvard are Thomas B. Kepler and Joseph G. Sodroski, respectively.

The study was funded with grants from the National Institute of Allergy and Infectious Diseases (AI0678501) (UM1-AI100645) and the Bill & Melinda Gates Foundation.

Sarah Avery | EurekAlert!
Further information:
http://www.duke.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>