IMMUNOGENIC SUBSTANCES IN CULTURE FILTRATES AND LYSATES OF PASTEURELLA TULARENSIS.

Hatch, Melvin T. (University of Utah, Salt Lake City), and Paul S. Nicholes. Immunogenic substances in culture filtrates and lysates of Pasteurella tularensis. J. Bacteriol. 88:566-573. 1964.-Culture filtrates and lysates of Pasteurella tularensis were tested for immunogenicity in mice subsequently infected with either strain 425 or 425 F4G. The efficacy of the vaccines varied with dosage and was significantly dependent upon methods of preparation. The optimal procedures for the production of an immunologically potent vaccine included: (i) aging the cultures after growth under partial anaerobiosis at 37 C, and (ii) inactivating the cells with phenol or formaldehyde. An unusual "survival phenomenon" was suggested when mice were administered large doses of cell-free vaccines and subsequently large doses of moderately virulent P. tularensis. The data indicated that the filtrates and lysates elicited an immune response sufficient to protect against an active infection with strains 425 or 425 F4G, and that the challenge dose per se stimulated an enhanced immunity. Furthermore, this survival phenomenon was demonstrable when immunized mice were subsequently given massive doses of strain 425 and challenged with approximately 1,000 ld(50) of the fully virulent strain Schu. On the basis of our data, we have hypothesized that the protective antigens were released into the suspending medium as a result of alterations in the permeability of cells undergoing either complete or partial enzymatic degradation. We believe that the envelope antigens were released from the cell by mechanisms analogous to those causing leakage of intracellular constituents in cells maintained at an incubation temperature in an unfavorable growth environment.