Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists explore new class of synthetic vaccines

26.07.2012
In a quest to make safer and more effective vaccines, scientists at the Biodesign InstituteÒ at Arizona State University have turned to a promising field called DNA nanotechnology to make an entirely new class of synthetic vaccines.

In a study published in the journal Nano Letters, Biodesign immunologist Yung Chang joined forces with her colleagues, including DNA nanotechnology innovator Hao Yan, to develop the first vaccine complex that could be delivered safely and effectively by piggybacking onto self-assembled, three-dimensional DNA nanostructures.

“When Hao treated DNA not as a genetic material, but as a scaffolding material, that made me think of possible applications in immunology,” said Chang, an associate professor in the School of Life Sciences and a researcher in the Biodesign Institute’s Center for Infectious Diseases and Vaccinology. “This provided a great opportunity to try to use these DNA scaffolds to make a synthetic vaccine.”

“The major concern was: Is it safe? We wanted to mimic the assembly of molecules that can trigger a safe and powerful immune response in the body. As Hao’s team has developed a variety of interesting DNA nanostructures during the past few years, we have been collaborating more and more with a goal to further explore some promising human health applications of this technology.”

The core multidisciplinary research team members also included: ASU chemistry and biochemistry graduate student and paper first author Xiaowei Liu, visiting professor Yang Xu, chemistry and biochemistry assistant professor Yan Liu, School of Life Sciences undergraduate Craig Clifford and Tao Yu, visiting graduate student from Sichuan University.

Chang points out that vaccines have led to the some of the most effective public health triumphs in all of medicine. The state-of-the-art in vaccine development relies on genetic engineering to assemble immune system stimulating proteins into virus-like particles (VLPs) that mimic the structure of natural viruses---minus the harmful genetic components that cause disease.

DNA nanotechnology, where the molecule of life can be assembled into 2-D and 3-D shapes, has an advantage of being a programmable system that can precisely organize molecules to mimic the actions of natural molecules in the body.

“We wanted to test several different sizes and shapes of DNA nanostructures and attach molecules to them to see if they could trigger an immune response,” said Yan, the Milton D. Glick Distinguished Chair in the Department of Chemistry and Biochemistry and researcher in Biodesign’s Center for Single Molecule Biophysics. With their biomimicry approach, the vaccine complexes they tested closely resembled natural viral particles in size and shape.

As proof of concept, they tethered onto separate pyramid-shaped and branched DNA structures a model immune stimulating protein called streptavidin (STV) and immune response boosting compound called an adjuvant (CpG oligo-deoxynucletides) to make their synthetic vaccine complexes.

First, the group had to prove that the target cells could gobble the nanostructures up. By attaching a light-emitting tracer molecule to the nanostructures, they found the nanostructures residing comfortably within the appropriate compartment of the cells and stable for several hours----long enough to set in motion an immune cascade.

Next, in a mouse challenge, they targeted the delivery of their vaccine cargo to cells that are first responders in initiating an effective immune response, coordinating interaction of important components, such as: antigen presenting cells, including macrophages, dendritic cells and B cells. After the cargo is internalized in the cell, they are processed and “displayed” on the cell surface to T cells, white blood cells that play a central role in triggering a protective immune response. The T cells, in turn, assist B cells with producing antibodies against a target antigen.

To properly test all variables, they injected: 1) the full vaccine complex 2) STV (antigen) alone 3) the CpG (adjuvant) mixed with STV.

Over the course of 70 days, the group found that mice immunized with the full vaccine complex developed a more robust immune response up to 9-fold higher than the CpG mixed with STV. The pyramid (tetrahedral) shaped structure generated the greatest immune response. Not only was immune response to the vaccine complex specific and effective, but also safe, as the research team showed, using two independent methods, that no immune response triggered from introducing the DNA platform alone.

“We were very pleased,” said Chang. “It was so nice to see the results as we predicted. Many times in biology we don’t see that.”

With the ability to target specific immune cells to generate a response, the team is excited about the prospects of this new platform. They envision applications where they could develop vaccines that require multiple components, or customize their targets to tailor the immune response.

Furthermore, there is the potential to develop targeted therapeutics in a similar manner as some of the new generation of cancer drugs.

Overall, though the field of DNA is still young, the research is advancing at a breakneck pace toward translational science that is making an impact on health care, electronics, and other applications.

While Chang and Yan agree that there is still much room to explore the manipulation and optimization of the nanotechnology, it also holds great promise. “With this proof of concept, the range of antigens that we could use for synthetic vaccine develop is really unlimited,” said Chang.

The work was supported by funding from the Department of Defense and National Institutes of Health (National Cancer Institute, National Institute of Drug Abuse).

Joe Caspermeyer | EurekAlert!
Further information:
http://www.asu.edu

More articles from Studies and Analyses:

nachricht Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

Im Focus: Virtual Reality for Bacteria

An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications

Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...

Im Focus: A space-time sensor for light-matter interactions

Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.

The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...

Im Focus: A transistor of graphene nanoribbons

Transistors based on carbon nanostructures: what sounds like a futuristic dream could be reality in just a few years' time. An international research team working with Empa has now succeeded in producing nanotransistors from graphene ribbons that are only a few atoms wide, as reported in the current issue of the trade journal "Nature Communications."

Graphene ribbons that are only a few atoms wide, so-called graphene nanoribbons, have special electrical properties that make them promising candidates for the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

Blockchain is becoming more important in the energy market

05.12.2017 | Event News

 
Latest News

Making fuel out of thick air

08.12.2017 | Life Sciences

Rules for superconductivity mirrored in 'excitonic insulator'

08.12.2017 | Information Technology

Smartphone case offers blood glucose monitoring on the go

08.12.2017 | Information Technology

VideoLinks
B2B-VideoLinks
More VideoLinks >>>