Navigation Links
Human trial proves ricin vaccine safe, induces neutralizing antibodies; further tests planned

Scientists have completed the first human clinical trial of a recombinant vaccine for the deadly toxin ricin ?a potential bioterror threat ?and the results indicate the vaccine is safe and effective in eliciting ricin-neutralizing antibodies, the UT Southwestern Medical Center researchers report.

The nearly year-long pilot study involved three groups of five volunteers each. Individuals in each group received a series of three injections of various doses of the vaccine, called RiVax, over the study period. As a recombinant vaccine, RiVax is a form of ricin that consists of a genetically modified subunit of the toxin, rather than an inactivated whole toxin.

All five of the individuals in the group receiving the highest vaccine dose produced ricin-neutralizing antibodies in their blood, indicating their immune systems had responded. Four of five in the intermediate dose group produced antibodies, while one of five in the lowest dose group did so.

The human-produced antibodies were then injected along with active ricin toxin into test mice, and the mice survived.

The results of the vaccine trial will be available this week online and in an upcoming issue of the Proceedings of the National Academy of Sciences.

"Our major concern in this trial was safety," said Dr. Ellen Vitetta, director of the Cancer Immunobiology Center at UT Southwestern and lead author of the study. "We have taken a very deadly toxin and genetically engineered it to be safe and to induce protective immunity in humans."

Dr. Vitetta's work with ricin received international attention when she and a team of UT Southwestern researchers in the Cancer Immunobiology Center developed the experimental vaccine for the deadly toxin as an outgrowth of their cancer-therapy work. Dr. Vitetta, Dr. Joan Smallshaw, assistant professor in the center, and their colleagues showed in pre-clinical studies that the subunit of the ricin toxin used to make RiVax was non-toxic b ut retained the capacity to elicit immunity.

Ricin, which can be administered in food and water or sprayed as an aerosol, is extracted from castor beans. There is currently no approved vaccine to prevent ricin poisoning in humans, and the biological agent has a long history of use in espionage.

Participants in the study, however, reported only mild side effects that were consistent with any intramuscular vaccine injection, such as a sore arm or mild headache that might be experienced with a tetanus or a flu shot, said Dr. Robert Munford, a professor of internal medicine and a collaborator on the study.

Based on the protection they observed in the mice injected with ricin mixed with human-produced antibodies, the researchers projected that a RiVax-vaccinated human could withstand a lethal dose of injected ricin. According to the Centers for Disease Control and Prevention, such a dose for an adult is as little as approximately 500 micrograms of ricin, an amount that would fit on the head of a pin.

The results from the UT Southwestern trial justify further development of the vaccine, Dr. Vitetta said.

"We have shown that this vaccine is safe and immunogenic," said Dr. Vitetta. "Now we need to tinker with the dose and formulation to give the longest-lasting and most robust immunity."

Antibodies were present in the blood of study participants for as long as 127 days after the last vaccine injection, but the longevity of the antibodies in a given volunteer was not related to the dose level of the vaccine he or she received. Dr. Vitetta and her colleagues are now conducting studies on mice that combine the vaccine with an adjuvant, a formulation that may lengthen the time the vaccine is effective. An adjuvant, such as alum, is an ingredient that enhances the immune response of a stand-alone vaccine. Other common vaccines, such as tetanus, are typically administered with an adjuvant and can confer immunity for years.

Dr. Smallshaw is currently determining whether the vaccine protects against aerosol and oral administrations in mice. "In a recent series of experiments, we have shown that the vaccine protects mice against lethal doses of ricin administered orally just as well as it protects them against injected ricin," she said. "We are also setting up an aerosol challenge model to determine the protective benefits of the vaccine."

Dr. Vitetta noted that, in humans, exposure by aerosol or food may require inducing immunity in the lung and gut by a very different formulation and vaccination schedule.

Depending on how the ricin is administered as a poison, 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 ?more than 50,000 tons of castor bean extract exist around the world as a byproduct of castor oil production ?public health officials warn that ricin could be used for terrorism. Indeed, there have been several incidents in recent years involving the toxin in the United States and Europe. The CDC classifies ricin as a "Category B" biological agent, which means it is "relatively easy to disseminate."

DOR BioPharma has received an exclusive license for RiVax and is developing large scale manufacturing processes. DOR officials hope 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.

Other UT Southwestern researchers from the Cancer Immunobiology Center involved in the study were Dr. John Schindler, assistant professor and director of clinical trials, and Dr. Elaine Coleman, senior research associate. Dr. Hasan Jafri, assistant professor of pediatrics, and Callie Foster, senior research nurse, also participated.


Source:UT Southwestern Medical Center

Related biology news :

1. FDA Approves Human Hookworm Vaccine for Phase I Safety Trials
2. New Clues Add 40,000 Years to Age of Human Species
3. Human Cells Filmed Instantly Messaging for First Time
4. Govt Creates Gene Database of Normal Human Tissues
5. Analysis Of Human Genome To Predict The Development Of Illnesses
6. Human Eggs Can Develop From Ovarian Surface Cells In Vitro
7. Determining The Fate Of Cells In The Human Body
8. Whole genome promoter mapping - Human Genome Project v2.0?
9. Human embryonic stem cells have the potential to develop into eggs and sperm in the laboratory
10. Going To Extremes To Improve Human Health
11. Human brain is still evolving
Post Your Comments:

(Date:9/28/2015)... , September 28, 2015 The ... to reach USD 12.03 billion by 2020, growing at ... advancements such as Backside Illumination (BSI) technique to improve ... the forecast period.      (Logo: , ... the chip to reduce loss and, thus, reduce the ...
(Date:9/24/2015)... 24, 2015  EyeLock LLC, a market leader of ... winning and latest technology in Booth #602 at next ... . EyeLock,s iris authentication technology provides an ... accuracy, making it the most proven way to authenticate ... technology to deliver a fast and friendly user experience ...
(Date:9/10/2015)... , Sept. 10, 2015 Report Details ... not quite delivered upon previous expectations of revenues, consumer ... the breakthrough year in which wearables begin to achieve ... One of the main reasons is the entrance of ... only the SmartWatches market, but the overall size of ...
Breaking Biology News(10 mins):
... Care through Bio and Information Standards and Technologies, a ... standards can play in helping the United States manage ... technology investments should be made to enhance health care ... WHEN: Tuesday 25 September, 8:30 a.m. to 5:30 ...
... in French . , Vancouver, B.C. - ... Natural Resources will speak at the UBCM Pine Beetle ... under the Mountain Pine Beetle Program to help affected ... Hotel, Mackenzie Room, 900 Canada Place Way, Vancouver, B.C. ...
... counselling on diet and lifestyle offers significant benefits to ... University Technology research. Dietitian Katrina Campbell, who graduated ... 62 pre-dialysis patients at the Royal Brisbane and Women,s ... part of her thesis. Dr Campbell said depending ...
Cached Biology News:
(Date:10/8/2015)... , Oct. 8, 2015  The ALS Association, in ... Assistive Technology Challenge to revolutionize communication technology solutions for ... --> ALS (amyotrophic lateral sclerosis) is a ... the brain and the spinal cord. Eventually, people with ... movement, which often leads to total paralysis and death ...
(Date:10/8/2015)...  Sigma-Aldrich Corporation (NASDAQ: SIAL ) announced ... its Applied Diagnostics and Testing business segment has ... line with ten certified Snap-N-Spike ® solutions ... their stable-labeled internal standards. These new solution certified ... acid and native and deuterium-labeled analogs of cholic ...
(Date:10/8/2015)... ... October 08, 2015 , ... ... fibrosis transmembrane conductance regulator (CFTR) gene and results in dysfunction of the lungs ... accumulates in the lungs. This mucus is very difficult to clear, blocks the ...
(Date:10/7/2015)... ... 2015 , ... Neil Riordan, PhD to Discuss Medicinal Effects of Mesenchymal Stem ... from 3:50 pm to 4:30 pm. , Dr. Riordan is one of the early ... is the Co-Founder and Chief Science Officer of the Riordan-McKenna Institute of ...
Breaking Biology Technology:
... and provides ... content not found elsewhere, MILFORD, Mass., Nov. 3 ... debut of an online community,designed to support the success of ... UltraPerformance,LC(R) (UPLC) System users worldwide, membership in this new online,community ...
... Neb. and GUELPH, Ontario, Nov. 3 ... an agreement to,distribute LI-COR biotechnology products in ... the local presence of Mandel Scientific skilled ... greatly enhance our ability to serve,our Canadian ...
... Albert Liou, Corporate Vice,President and General Manager, Asia-Pacific ... a leading global,biopharmaceutical services provider, will present "What ... Efficiency Savings in Running Clinical,Trials?" at the 7th ... be held November 4 - 7, 2008 at ...
Cached Biology Technology:
... Grade Thrombin is a highly purified preparation ... with appropriate vectors. The preparation is functionally ... is free of detectable contaminating proteases. Prepared ... by certified tests to be negative for ...
Rat Cardiac Fibroblasts (RCF) (>500,000 cells)...
Rat Aortic Smooth Muscle Cells (RAOSMC) (>500,000 cells)...
Biology Products: