Role of antibody in vaccine-mediated protection against pneumonic tularemia in the rabbit model

Abstract

Abstract Francisella tularensis, a gram negative coccobacillus, is the causative agent of tularemia, a severe zoonotic infection. When inhaled, as few as 15 cfu is sufficient to cause disease. There is concern that tularemia could be used as a biological weapon so vaccines are urgently needed. We have previously shown that the New Zealand White (NZW) rabbit is a good model of human disease; after exposure to small particle aerosols containing virulent F. tularensis at doses as low as 66 cfu, naive NZW rabbits develop fever within 3 days and succumb within 4–7 days. Disease pathology in the NZW rabbit strongly resembles what has been reported in humans. Recombinant derivatives of a virulent strain of F. tularensis are highly attenuated in NZW rabbits and protect against aerosol challenge with virulent F. tularensis. The level of protection is dependent on the strain used, the route of vaccination, and the number of vaccinations. Using a prime-boost small particle aerosol vaccination regimen, 73% percent of rabbits survived a robust (100 LD50) challenge when vaccinated with a strain that is deficient in the aromatic amino acid synthase pathway. Pre-challenge, post-vaccination plasma IgG and IgM titers against heat-killed F. tularensis correlate with protection. A single inoculation of plasma from hyper-immune rabbits extended the survival of naïve rabbits by one day. We will report our efforts to evaluate the role of antibody in protection of NZW rabbits against tularemia, including passive immunization of mice using purified immunoglobulin from hyper-immune rabbits and in vitro assays of antibody function.