Successful treatment of bacterial infection hinders development of acquired immunity

Antibiotics are routinely used to control bacterial infection, but the acquisition of acquired immunity following successful treatment has rarely been examined. We developed a model that allows visualization of acquired immunity during and following antibiotic treatment of typhoid. Pathogen-specific humoral and cellular immune responses were activated rapidly in antibiotic-treated mice, but were not sustained after successful antibiotic treatment and did not confer protection to secondary infection. In marked contrast, pathogen-specific Th1 and Ab responses matured over several weeks following immunization with a live vaccine strain. The deficiency in protective immunity following antibiotic treatment could be overcome by administering flagellin during antibiotic therapy. Thus, development of protective immunity is hindered by rapid therapeutic elimination of bacteria, but can be overcome by providing additional inflammatory and/or antigenic stimuli.