Live-Attenuated and Inactivated Whole-Cell Bacterial Vaccines

Abstract

Pathogen attenuation to allow its safe administration to protect otherwise susceptible subjects from infection is one of the earliest principles of vaccinology. At the same time that the first live-attenuated vaccines were developed, immunization with killed bacteria was being explored. Thus, live-attenuated and inactivated whole-cell bacterial vaccines are the oldest human vaccines still in use today. Live-attenuated bacterial vaccines currently in use are Bacille Calmette-Guerin (BCG) vaccines that have demonstrated effectiveness in preventing disseminated childhood tuberculosis and that are still used to immunize newborns worldwide; and a typhoid vaccine that is used primarily as a traveler’s vaccine. Killed whole-cell bacterial vaccines still in use are Bordetella pertussis vaccines which continue to be administered to prevent whooping cough to the majority of the global birth cohort, particularly in low-income countries; and cholera vaccines which are used mainly by travelers to endemic areas, and to a lesser extent to control infections in endemic or epidemic settings. The production of live-attenuated and killed vaccines has been troubled historically by issues of quality and poor efficacy. Incomplete attenuation is associated with the risk of acute infection and disease by the vaccine strain. Production of inactivated vaccines of inconsistent potency and quality has led to outbreaks of disease in countries where vaccines of low potency have been used. Serological correlates of protection have not been identified. New approaches to prevent these bacterial diseases, including the development of live genetically attenuated vaccines are under development.