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 Investigators may unlock mystery of how staph cells dodge the body's immune system
22.09.2017 | Cedars-Sinai Medical Center

nachricht Monitoring the heart's mitochondria to predict cardiac arrest?
21.09.2017 | Boston Children's Hospital

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>