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 Nanotubes built from protein crystals: Breakthrough in biomolecular engineering
15.11.2018 | Tokyo Institute of Technology

nachricht Insect Antibiotic Provides New Way to Eliminate Bacteria
15.11.2018 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

Im Focus: Coping with errors in the quantum age

Physicists at ETH Zurich demonstrate how errors that occur during the manipulation of quantum system can be monitored and corrected on the fly

The field of quantum computation has seen tremendous progress in recent years. Bit by bit, quantum devices start to challenge conventional computers, at least...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Massive impact crater from a kilometer-wide iron meteorite discovered in Greenland

15.11.2018 | Earth Sciences

When electric fields make spins swirl

15.11.2018 | Physics and Astronomy

Discovery of a cool super-Earth

15.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>