Their findings, published in the July 26 issue of the journal Immunity, could result in more potent vaccines that are relatively inexpensive to produce, easy to store, and that can be transported without refrigeration.
In experiments with mice, the researchers, led by Eyal Raz, M.D., Professor of Medicine at UCSD's School of Medicine and Joshua Fierer, M.D., UCSD Professor of Medicine and Chief, Infectious Diseases Section, VA San Diego Healthcare System, demonstrated that a vaccine made with irradiated Listeria monocytogenes (LM) bacteria provided much better protection against disease than vaccine made from heat-killed bacteria. Listeria is a food-borne pathogen that can cause severe meningitis and systemic illness in immuno-compromised individuals. It is on a list of agents that could potentially be used in bioterrorist attacks, compiled by the National Institutes of Health.
To test the irradiated LM, mice were vaccinated with either heat-killed or irradiated vaccine, and then given lethal doses of LM bacteria. All of the unvaccinated or heat-killed vaccinated mice died, but 80% of those vaccinated with the irradiated vaccine survived. Protection against infection lasted more than one year after vaccination with irradiated LM.
"Irradiation is a technically simple process that retains structural features of the bacterial pathogen without destroying the natural antigens or the intrinsic adjuvants. Therefore, a strong immune response is induced in the vaccinated host," said Sandip Datta, M.D., assistant professor in UCSD's Department of Medicine and lead author of the study.
The inactivation, or attenuation, of pathogens has been a strategy for vaccine development since Louis Pasteur first attempted vaccinations nearly 150 years ago. Vaccines are designed to stimulate the immune system to protect against micro-organisms such as viruses or bacteria, by introducing a small amount of the virus or bacteria into the body. When this foreign substance invades the body, the immune system activates certain cells to destroy the invader. If the body is re-invaded by the virus or bacteria in the future, the memory cells will be reactivated and respond faster and more powerfully to destroy the virus.
Immunization with attenuated live micro-organisms promotes a strong immune response, but there are safety, storage and transportation issues with these live vaccines. Immunizations using killed bacteria are very safe, but they don't work as well in eliciting a protective immune response.
"Irradiation destroys the DNA, making the bacteria unable to replicate so it cannot establish an infection," said Raz. "But some residual metabolic activity may survive, so the irradiated bacteria can still find its natural target in the host."
The researchers further showed that, unlike heat-killed bacteria, irradiated bacteria retain the ability to activate the immune system through Toll-like receptors. Toll-like receptors detect signature molecules produced by microbes and help hosts recognize they are under attack by bacteria and trigger an inflammatory response against the bacteria. These receptors are the "sentinels" of the body's innate immune system, and they activate the acquired immune system that provides long-term, specific immunity against a pathogen. The ability of Listeria to activate these receptors appears to be intact after gamma-irradiation.
The researchers speculate that heat-killed bacteria may target an entirely different pathway, because the bacterial molecules that engage these surface cell receptors have been destroyed.
Vaccination with a freeze-dried powder formulation of the irradiated bacteria– a product with the potential to be easily and inexpensively stored and transported, then reconstituted just before use – was also shown to protect mice against lethal infection.
These findings could result in the mass production of more affordable, more effective vaccines for resource-poor regions where vaccines are most needed. The technology could also greatly expedite vaccine production and distribution during epidemic outbreaks, bioterrorist attacks or other biothreats, according to the researchers.
"The resulting vaccines using irradiation might be the next-best approach, after those produced using live bacteria. But they would be very safe, simple and inexpensive to produce," said Raz. "This might not be the ideal vaccine, but its practicality is beyond imagination."
The research team is experimenting with several other bacterial strains in addition to LM. They noted that there is a potential that the process may also work to produce a vaccine against Staphylococcus aureus, an important human pathogen that causes drug-resistant staph infections.
Debra Kain | EurekAlert!
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences