Medical Device Daily

Here comes the neutron bomb for vaccines.

A paper published in the July issue of the Journal Immunity reports that researchers were able to preserve the immunogenicity of the bacterium Listerium monocytogenes by irradiation, leaving them with a dead vaccine that produced a strong immune response, including a T-cell response.

“One of the limitations of vaccines is that killed vaccines aren't as immunogenic as live vaccines,” first author Sandip Datta told Medical Device Daily's sister publication, BioWorld Today. “But with live vaccines, we always worry that they will cause the disease they are meant to prevent. Now here's a killed vaccine that can elicit a T cell response” – meaning it could be stronger than vaccines made from heat-killed bacteria or bacterial fragments, but safer than live attenuated vaccines.

Why irradiation works as well as it does is still unclear, but Datta said that “the simplest explanation that we have is that irradiation kills them but leaves intact a lot of their surface structure.”

In contrast, heat-killing, the current preferred method for offing vaccine components, destroys such surface structure, rendering the bacteria less recognizable to the immune system.

Irradiation has been used before to kill bacteria for use in vaccines and is actually in use now for some veterinary vaccines. However, the procedure, which is used on parasites more than bacteria in veterinary applications, usually doesn't quite kill the organism. Instead, it weakens it enough to prevent it from causing a full-scale infection; the infection stalls in the early stages, hence progressing just far enough to cause an immune response.

The researchers at the University of California, San Diego and the San Diego Veterans Affairs Medical Center (both La Jolla, California) first tested the effectiveness of irradiated bacteria in a vaccine by vaccinating mice with either irradiated or heart-killed bacteria and then infecting them with high doses of Listeria four weeks later.

While all the mice that were vaccinated with heat-killed bacteria, as well as all unvaccinated controls, died, the group that had been vaccinated with irradiated bacteria had an 80% survival rate.

The researcher investigated the cellular pathways that were being activated by the irradiated bacteria. Cells that were deficient in several types of toll-like receptors or MyD88, an adaptor molecule that is necessary for most toll-like receptor-mediated signaling, also showed a deficient innate immune response to the irradiated Listeria. But “other aspects of the immune response were intact,” Datta said – notably, the vaccine was still able to elicit both killer and helper T cell responses.

Besides the safety advantages of using killed bacteria, the irradiated Listeria also seem to have an advantage when it comes to practicality: The scientists found that mice could be protected by vaccination with irradiated Listeria that had been freeze-dried into a powder.

Live, attenuated vaccines must be kept refrigerated at all times to prevent them from spoiling – something that is not a great problem in the U.S. but is a big problem in developing nations where vaccines are most desperately needed.

If the technique pans out, freeze-dried vaccines made from whole, irradiated bacteria could be reconstituted from powder directly before use – no cooling necessary