Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UT Southwestern initiating trials in humans for ricin vaccine

30.11.2004


A potential vaccine for the deadly toxin ricin, a "Category B" biological agent, will enter the first phase of clinical testing in coming weeks at UT Southwestern Medical Center at Dallas.



The Food and Drug Administration and the UT Southwestern Institutional Review Board have agreed that the trial can go forward in humans. "This is a safety and immunogenicity trial," said Dr. Ellen Vitetta, director of the Cancer Immunobiology Center at UT Southwestern. "To test the immune response induced by the vaccine, the sera (blood products) from our injected human volunteers will be tested for levels of specific ricin-neutralizing antibodies. These antibodies, in turn, will be evaluated for their ability to protect mice against a lethal ricin challenge. As far as we can tell, the vaccine is completely safe and has no side effects."

Dr. Vitetta’s work with ricin received international attention when she and a team of UT Southwestern researchers developed an experimental vaccine for the deadly toxin as an outgrowth of their cancer-therapy work. The translation from discovery to clinical testing has moved rapidly with support from the National Institutes of Health (NIH) and the "incredible efforts of a talented and dedicated group of scientists and research associates," Dr. Vitetta said.


The genetically engineered protein vaccine, RiVax, was developed by Dr. Vitetta and the center’s Drs. Victor Ghetie, professor; Joan Smallshaw, assistant professor; and John Schindler, assistant professor and director of the clinical trial.

Ricin, which can be administered in foods and water or sprayed as an aerosol, is extracted from castor beans. There is currently no effective vaccine or treatment for ricin poisoning in humans.

Depending on how the ricin is administered, victims develop fever, nausea and abdominal pain or lung damage before dying within a few days of exposure. There is no antidote after the first few hours of exposure, and because symptoms do not appear until later and often mimic other illnesses, individuals often do not know if they have been exposed until it is too late for treatment, Dr. Vitetta said.

Because castor beans are readily available, public health officials warn that ricin could be used for terrorism. Indeed, ricin has a long history of use in espionage, and there have been several recent incidents involving the toxin in the United States and Europe. The Centers for Disease Control classifies ricin as a "Category B" biological agent, which means it is "relatively easy to disseminate."

In creating the new vaccine, Dr. Smallshaw mutated the DNA encoding the active "A" chain of the toxin. She deleted the site in this chain that inhibits the cell’s ability to synthesize proteins, as well as the site responsible for inducing vascular leak in the host. UT Southwestern scientists eventually created three genetically distinct non-toxic versions of the ricin A chain, two of which were effective as vaccines in mice. Dr. Vitetta said E. coli bacteria are used to produce the A chain protein, making vaccine production inexpensive and safe.

The DNA sequence was identified by Dr. Vitetta’s group several years ago in its ongoing efforts to produce safer immunotoxins containing the A chain of ricin. Dr. Vitetta and her colleagues have used such immunotoxins – anti-cancer drugs – as experimental therapy in more than 300 cancer patients.

Injected RiVax protects mice against 10 lethal doses of ricin and has no side effects in mice when given at 100 times the dosage required for an immune response. A similar study in rabbits also showed no side effects, and the animals also produced high levels of ricin-neutralizing antibodies, Dr. Vitetta said.

The pilot phase I trial – to be carried out by Dr. Robert Munford, professor of internal medicine and microbiology – is designed to confirm the vaccine’s safety at doses that induce effective antibody levels in healthy humans. DOR BioPharma, Inc. has received an exclusive license for the vaccine and is developing manufacturing processes for the genetically engineered vaccine. DOR is planning to produce a large stockpile for more advanced human clinical testing, product licensing and potential purchases from the U.S. government and other interested parties. "I am confident that DOR will move the vaccine forward rapidly and effectively after our trial is completed, assuming that the vaccine is safe," Dr. Vitetta said.

"Our future work here at UT Southwestern will focus on how to deliver the vaccine by oral or intranasal routes instead of by injection," she said. "Mucosal immunity is fascinating and extremely important for virtually all types of biothreats because most will be inhaled or ingested. It is important to have immunity at these anatomical sites and not only in the blood. The blood may prevent death but not tissue damage in the lungs, intestine and elsewhere."

Amanda Siegfried | EurekAlert!
Further information:
http://www.utsouthwestern.edu

More articles from Health and Medicine:

nachricht Improving memory with magnets
28.03.2017 | McGill University

nachricht Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: A Challenging European Research Project to Develop New Tiny Microscopes

The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.

To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...

Im Focus: Giant Magnetic Fields in the Universe

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...

Im Focus: Tracing down linear ubiquitination

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...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Transport of molecular motors into cilia

28.03.2017 | Life Sciences

A novel hybrid UAV that may change the way people operate drones

28.03.2017 | Information Technology

NASA spacecraft investigate clues in radiation belts

28.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>