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!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy