Vaccines against facultative intracellular pathogens are disclosed. A host is vaccinated with non-viable but metabolically active agents. The non-viable agents produce immunogenic components that elicit protective host immune responses, with minimal likelihood of host infection by the vaccine agent. Living agents, either attenuated or virulent, are exposed to a dose of gamma irradiation (or other strong mutagen) that is sufficient to limit or prevent the replication of the agents within the host, but that is insufficient to stop the metabolic activities of the agent. In vitro exposure of a microbial agent to the damaging effects of gamma irradiation or of another strong mutagen induces certain stress responses in the infectious agent. These stress responses are similar to the stress responses that the virulent agent would produce within the tissues of the host. The stress responses include the production of antigens that stimulate appropriate host immune responses when the irradiated agent is used in a vaccine. Examples of facultative intracellular pathogens for which non-viable vaccine agents may be made in accordance with the present invention include various bacterial pathogens (e.g., Brucella sp., Brucella abortus, Mycobacterium sp., Mycobacteriun lepraemurum, Mycobacterium tuberculosis, Salmonella sp., Salmonella typhimurium); various mycotic pathogens (e.g., Blastomyces, Histoplasma, Cocidioides); and various protozoal pathogens (e.g., Leishmania, Trypanosomas).