Respiratory tularemia: comparison of selected routes of vaccination in Fischer 344 rats

Abstract

Fischer 344 rats were given the attenuated live vaccine strain of Francisella tularensis by small-particle aerosol, intranasal instillation, or intraperitoneal, intramuscular, or subcutaneous injection. All of the vaccinated rats developed subclinical infection by 3 days after exposure, which cleared by day 28. Temporal patterns and concentrations of the live vaccine strain organism within the hosts were dependent on the route of vaccination. Pathological alterations were limited to minimal lung lesions in aerosol-vaccinated rats and mild splenitis in intraperitoneally vaccinated rats. Agglutinins to live vaccine strain were detected in the serum of each vaccinated animal and in the bronchoalveolar wash fluids of 66% of the aerosol-vaccinated rats. Agglutinin activity of the vaccinated rats was associated predominantly with the immunoglobulin M class. Regardless of the route of vaccine administration, all vaccinated rats survived an aerosol challenge of 5.3 log10 cells of virulent F. tularensis, whereas all nonvaccinated rats died. Systemic infection did not occur in the vaccinated rats. Pulmonary infection was not prevented in the vaccinated rats after aerosol challenge, but proliferation of the virulent F. tularensis organisms in the lungs was significantly lower (analysis of variance, P less or equal to 0.01) than that which occurred in the control animals. These studies demonstrate the utility of the inbred Fischer 344 rat as a model host for further investigations of F. tularensis infection and its associated immune response.