World's Toughest Bacterium Holds Promise for Rapid Vaccine Development Against Deadly Diseases

A lethally irradiated vaccine was successfully tested in mice against drug-resistant Staphylococcus aureus bacteria by colleagues at the National Institutes of Health (NIH), and holds promise for other such deadly diseases.

High doses of radiation typically destroy a pathogen’s genome, rendering it unable to cause infection when used in a vaccine. However, radiation also damages a microbe’s protein epitopes, which the immune system must recognize for a vaccine to be protective. Organisms inactivated, or killed, by radiation trigger better immune responses than those inactivated by traditional heat or chemical methods. Although live vaccines may provide better immune protection than irradiated vaccines, live vaccines are frequently not an option as they can carry an unacceptable risk of infection with an otherwise untreatable disease (e.g., HIV). Lethally irradiated vaccines could also help the developing world, where the need for cold storage limits the availability of live vaccines.

To separate genome destruction from epitope survival, the researchers borrowed some complex chemistry from the world’s toughest bacterium Deinococcus radiodurans, nicknamed “Conan the Bacterium,” which can withstand 3,000 times the radiation levels that would kill a human being. In 2000, Deinococcus was engineered for cleanup of highly radioactive wastes left over from the production of atomic bombs. Now, unusual Mn(II)-antioxidants discovered in this extremophile have been successfully applied to preparing irradiated vaccines.

Deinococcus accumulates high concentrations of manganese and peptides, which the scientists combined in the laboratory —forming a potent antioxidant complex which specifically protects proteins from radiation. They found that the complex preserves immune-related epitopes when applied to viruses and bacteria during exposure to gamma radiation, but did not protect their genomes.

Michael J. Daly, Ph.D., and his research team from USU collaborated on the work with Sandip K. Datta, M.D., and colleagues at NIH’s National Institute of Allergy and Infectious Diseases (NIAID).

The scientists used the Mn-peptide complex in a laboratory setting to successfully protect from radiation damage the protein epitopes of Venezuelan equine encephalitis virus, a microbe that causes a mosquito-borne disease of the nervous system. They also used the preparation method to develop an effective vaccine against methicillin-resistant S. aureus (MRSA) infections in mice.

The researchers believe the whole-microbe vaccine approach could extend to any infectious organism that can be cultivated, whether fungi, parasites, protozoa, viruses or bacteria—including agents that mutate rapidly, such as pandemic influenza and HIV. The groups aim to demonstrate this method of irradiation as a rapid, cost-effective approach to vaccine development.

The project was funded by the Air Force Office of Scientific Research (AFOSR) and the intramural research program of the NIAID. For more information on Deinococcus research, visit

http://www.usuhs.mil/pat/deinococcus/index_20.htm. For information on AFOSR, contact Dr. Hugh DeLong (hugh.delong@afosr.af.mil).

ARTICLE:
The results of the breakthrough study titled “Preserving Immunogenicity of Lethally Irradiated Viral and Bacterial Vaccine Epitopes Using a Radio-Protective Mn2+-Peptide Complex from Deinococcus” will be published in the July edition of Cell Host and Microbe.
WHO:
Michael J. Daly, Ph.D., Professor, Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, is the study lead author. He has devoted 20 years to studying Deinococcus radiodurans, which has led to three patents for his work.

Sandip K. Datta, M.D., Lead Clinical Investigator, Bacterial Pathogenesis Unit, NIAID Laboratory of Clinical Infectious Diseases. Dr. Datta is an expert in immune responses against bacteria and vaccines.

CONTACT:
To schedule interviews with Dr. Daly, please contact Sharon Willis, (301)295-1219, Sharon.willis@usuhs.edu, or Gwendolyn Smalls, (301) 295-3981, Gwendolyn.smalls@usuhs.edu.

The Uniformed Services University of the Health Sciences (USU) is the nation’s federal health sciences university. USU students are primarily active duty uniformed officers in the Army, Navy, Air Force and Public Health Service who have received specialized education and training in tropical and infectious diseases, preventive medicine, the neurosciences (to include TBI and PTSD), disaster response and humanitarian assistance, and acute trauma care. A large percentage of the university’s more than 4,800 physician and 600 advanced practice nursing alumni are also supporting operations in Afghanistan and elsewhere, offering their leadership and expertise. USU also has graduate programs in biomedical sciences and public health, open to civilian and military applicants committed to excellence in research.