Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeted DNA vaccine may reverse autoimmune disease

11.08.2003


Stanford University Medical Center researchers have developed a way to tailor therapies to combat the specific inappropriate responses of autoimmune diseases in mice. The researchers also have shown that their technique can provide information needed to predict a disease’s progression. Eventually, their work may provide a way to reverse the course of such autoimmune diseases in humans as multiple sclerosis, rheumatoid arthritis and type-1 diabetes by first identifying the immune system culprits gone awry and then creating customized therapies for individual patients.



Researchers Bill Robinson, P. J. Utz and Lawrence Steinman published results last year showing how microarrays - glass slides spotted with minute amounts of the proteins against which the body may be reacting - can provide a profile of the antibodies’ targets. Their current work, which appears in the September issue of Nature Biotechnology, takes the technology a step further and shows that the pattern of antibody activation can be used to predict and treat animals suffering from a disease resembling M.S.

"Ultimately, we think the array can be used to guide patient-specific therapy," said Robinson, MD, PhD, assistant professor of medicine (immunology and rheumatology) and lead author of the study. For example, a blood sample from a patient thought to have M.S. could be profiled using the array to help identify whether the person is likely to progress to full-blown disease and whether the individual would benefit from therapy. The information obtained in the profile could then be used to personalize therapies.


The team, which included former Stanford researcher Hideki Garren, MD, PhD, showed that this strategy works in a mouse model of M.S. called experimental autoimmune encephalomyletis, or EAE. In both conditions, the immune system launches an attack against the myelin sheath, the fatty cells that insulate neurons from electricity and ensure the speedy transmission of nerve impulses. Neurons that have patches of myelin destroyed by M.S. or EAE short-circuit and can lead to a variety of neurological disorders, depending on the part of the brain affected.

"Looking at one M.S. marker at a time had previously not been terribly informative," said Robinson. "We thought that looking at thousands at once would be more fruitful." Thanks to a dozen or so labs around the world that shared their protein samples, the group rapidly produced a comprehensive array that covered hundreds of the myelin sheath proteins.

When they analyzed serum samples from EAE mice using the array, they found that each mouse had a unique pattern of reactivity. Based on their antibody profiles, mice whose immune systems were attacking more elements on the myelin sheath progressed to a more severe disease, while mice whose immune systems made more restricted responses did not progress and had fewer flare-ups. The group then designed a treatment to reverse the progression of the disease, treating mice that had already suffered an initial attack of paralysis.

Autoimmune responses are thought to develop when antibodies attack many different proteins in the organ being targeted, so Robinson and his colleagues wanted to find a therapy that specifically knocked out as many of the harmful responses as possible while leaving the rest of the immune system functional. To do so, they took advantage of a well-known but poorly understood process known as tolerization. In this process, the immune system is coaxed to tolerate an offending protein after injection of that same protein or pieces of it. Utz, MD, assistant professor of medicine (immunology and rheumatology), likens the process to allergy shots: the agent causing the allergic reaction is injected into muscle in order for the body to learn to ignore it.

Using the microarray information to guide them to the targets of the autoimmune response in the sickest mice, Garren and Steinman, MD, professor of neurology and neurological sciences, built on previous studies in Steinman’s lab to create a tolerizing vaccine that delivered four of the targeted proteins. To make an effective delivery vehicle, they put the DNA sequence that encoded the proteins into a circular piece of DNA called a plasmid, creating a DNA vaccine. When these engineered plasmids were injected, they produced the desired proteins and a programmed tolerization process began.

One advantage of DNA vaccines over other methods of tolerization, Garren noted, is that it allows for multiple autoimmune targets to be tolerized simultaneously rather than one at a time. "We found that this approach broadly turns off autoimmune responses," said Robinson. "Clinically, the animals do better when receiving the vaccine. When we use our arrays to monitor the response, we see broad reductions in the progression of the disease."

The ability to profile which antibodies have gone awry has a number of implications for diagnosis and treatment of people with autoimmune diseases. "When we see these patients, we have no idea what is going to happen 10 years from now," Utz said. "It would be great to have a test that would let us know if a person is going to have a horrible outcome so we could treat aggressively, or if a person is going to be fine, or if a person is going to have a bad response to a therapy so we could avoid that."

Led by Steinman, the team plans to use their findings to help people with autoimmune diseases. To reach this goal, they co-founded Bayhill Therapeutics; Garren directs the scientific efforts of the company.

Using DNA vaccines to specifically turn off the immune system is a completely new way to immunize, said Steinman. "This is the opposite of what we try to do with traditional vaccines against bacteria and viruses, where we want to stimulate the immune system to attack the microbe," he added.

This study was funded by a number of sources, including funds from a $14.7 million contract from the National Institutes of Health, the Baxter Foundation and the Arthritis Foundation.

Mitzi Baker | EurekAlert!
Further information:
http://mednews.stanford.edu

More articles from Life Sciences:

nachricht Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University

nachricht How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>