Vaccines made with bacteria killed by gamma irradiation, rather than by standard methods of heat or chemical inactivation, may be more effective, say researchers supported by the National Institute of Allergy and Infectious Diseases (NIAID).
Vaccines made from gamma-irradiated bacteria also may not need to be kept cold; an advantage in settings where refrigerating vaccines is impractical or impossible. A report on the research appears in the current issue of the journal Immunity.
In experiments with mice, scientists including Eyal Raz, M.D., Sandip Datta, M.D., and Joshua Fierer, M.D., of the University of California, San Diego, School of Medicine demonstrated that a vaccine made from irradiated Listeria monocytogenes bacteria, unlike a vaccine made from heat-killed bacteria, provides protection against challenge with live Listeria. The irradiated bacteria also stimulated a protective response from immune system cells called T cells. Previously, only vaccines made from live, weakened Listeria bacteria were believed capable of eliciting a T-cell response.
"This advance is potentially of great importance in meeting the challenge of creating vaccines that are safe, effective and simple to manufacture and transport," says NIH Director Elias A. Zerhouni, M.D.
Ideally, vaccines should stimulate a strong response not only from both arms of the adaptive immune system (antibodies and T cells), but also the body's innate immune system. However, traditional ways of making vaccines - either by killing disease-causing agents with heat, chemicals or by weakening (attenuating) live pathogens - have characteristic shortcomings. For example, heat- and chemical-killed vaccines, while safe and relatively easy to produce, generally produce a less broad immune response than live, attenuated vaccines. Conversely, it can be difficult to create live, attenuated vaccines that safely preserve the pathogen's ability to trigger strong innate and adaptive immune responses.
"By showing that whole, irradiated bacteria can form the basis of a vaccine that elicits a strong response from both arms of the adaptive immune system, Dr. Raz and his colleagues have opened the possibility of making a variety of bacterial vaccines that combine the best features of both killed-agent and live, attenuated vaccines," says NIAID Director Anthony S. Fauci, M.D.
Earlier research in Dr. Raz's laboratory had shown that irradiated probiotics (bacteria that are beneficial to health) retain the ability to trigger innate immune system responses via proteins called toll-like-receptors. Based on that observation, says Dr. Raz, "we hypothesized that a vaccine made from whole, irradiated bacteria would retain the properties needed to evoke a broad immune response and result in a superior vaccine compared with other methods of killing the pathogen."