Vaccines made with bacteria killed by gamma rays may be more effective than those made using standard heat or chemical inactivation, according to Sandip Datta, MD, assistant professor in the department of medicine at the University of California, San Diego (http://www.ucsd.edu). These were among the findings published in the July 26 issue of Immunity.
Killing organisms by gamma-irradiation retains their immunogenic properties better than other methods of killing (e.g., heat or chemical inactivation), says Datta. Therefore, this opens the possibility of developing killed vaccines that approach the efficacy and immunogenicity of live attenuated vaccines, while retaining the safety profile of killed vaccines.
Datta and colleagues made a vaccine from Listeria monocytogenes bacteria, a common cause of food poisoning, which can also lead to meningitis and systemic illness in immuno-compromised individuals. The Listeria, which the NIH says could be used in terrorist attacks, were killed with gamma rays; yet the vaccine protected mice infected with live Listeria.
“In theory, lethal gamma-irradiation of whole organisms could be used to create vaccines against any bacterial pathogen, and possibly even against viruses,” says Datta. “In addition to Listeria, potential bacterial candidates include important causes of diarrheal illness such as typhoid (Salmonella typhi), Shigella, Campylobacter, and Vibrio cholera. Mycobacterium tuberculosis is another potential target.” Datta points out that Staphylococcus aureus and other bacteria that are becoming difficult to treat because of antibiotic resistance would also be good candidates for vaccine development.
A recent trend in vaccine development is using subunit vaccines (e.g., hepatitis B vaccine) that use recombinantly produced parts of the pathogen. However, quite a few killed whole organism vaccines are still in use, says Datta. These include the Diphtheria-Pertussis-Tetanus vaccine, the Pneumococcal vaccine (Pneumovax), and the Hepatitis A vaccine. Subunit vaccines have many of the same limitations as killed whole vaccines, Dr. Data says. “They are relatively poorly immunogenic compared to live attenuated vaccines.”
In addition to increasing vaccine effectiveness, making vaccines with bacteria killed by gamma rays has practical advantages.
“Vaccine development can be simplified and made less expensive,” says Datta. Because whole organisms can be irradiated, developing these vaccines will not require the time-consuming and expensive processes of identifying antigenic components and adjuvant formulations that are needed to develop subunit vaccines, or creating genetic mutants for live attenuated vaccine strains. Additionally, growing and irradiating large quantities of bacteria to prepare the vaccine is a relative simple and inexpensive process. This should lead to more rapid development and production of vaccines in situations such as epidemic outbreaks or bioterrorist threats.
Transporting vaccines also can be made less expensive. “Killed vaccines are more stable than live vaccines,” says Datta. “So, using killed irradiated vaccines will decrease the costs of refrigerating a vaccine during storage and transportation ('the cold chain').” Lyophilization of the vaccine into a powder formulation that can be later reconstituted should further increase stability.
Transportation costs add significantly to the cost of administering vaccines in resource-poor areas of the world, so this advantage should make vaccines more widely accessible to the people who need them.