Respiratory Immunity is a Critical Component of Protection Elicited by Subunit Vaccination Against Pneumonic Plague

摘要

Mice were vaccinated with a recombinant fusion protein, rF1-V, by an intramuscular prime followed by an intranasal boost, to evaluate protection against pneumonic plague. Forty-two days after the intranasal boost, the mice were challenged by aerosol exposure to Yersinia pestis. Only at the highest doses of rF1-V given intranasally was survival comparable to prior studies of rF1-V given by two intramuscular doses (> or = 8805;80% survival). Pulmonary and serum antibody titers to V correlated well with outcome. For vaccinated mice that succumbed to the infection, death was delayed by 1-2 days compared to sham- inoculated controls. Weight loss correlated with outcome. Pathology studies indicated a severe, necrotizing bronchopneumonia in vaccinated mice that were euthanized or died, compatible with a prolonged disease course, while the lungs of sham-inoculated mice had only mild pneumonia, which is compatible with a more rapid disease course. Immunity in the respiratory tract appears to be critical for protection against primary pneumonia caused by Y. pestis.