Selectively disrupted whole-cell vaccine
The present invention provides for immunogenic compositions and methods for producing an immunogenic composition with multiple immunity-inducing fractions of killed, whole-cell Streptococcus pneumoniae by selectively disrupting a whole cell bacterial preparation in such a manner that a soluble fraction that induces a primarily antibody response, and a cellular fraction that induces a primarily antibody-independent response, remain in the immunogenic composition.
1. A method for producing a killed, whole-bacterial immunogenic composition from Streptococcus pneumoniae which elicits an antibody-mediated immune response and a T-lymphocyte mediated immune response, comprising
(i) selectively disrupting the Streptococcus pneumoniae bacteria in a bacterial preparation into a soluble fraction and an insoluble fraction using a solvent that is at least one of: an immiscible solvent, a volatile agent which evaporates at room temperature, or beta-propiolactone whereby the solvent maintains the overall structure of the Streptococcus pneumoniae bacterial cell,
(ii) removing the solvent by evaporation, hydrolysis or lyophilization or heat inactivation at 37° C. such that the soluble fraction is not removed from the bacterial preparation and both the soluble and cellular fraction remain in the immunogenic composition and wherein the bacterial cell preparation is not washed;
(iii) resuspending the bacterial preparation in an aqueous solution comprising an adjuvant, wherein the soluble fraction elicits an antibody-mediated immune response, and the cellular fraction elicits a T-lymphocyte mediated immune response.
2. The method according to claim 1 , wherein said soluble fraction induces a serotype-independent antibody response, and said cellular fraction induces increased phagocytosis.
3. The method according to claim 1 , wherein the immiscible solvent or volatile agent which evaporates at room temperature is chloroform or trichloroethylene.
4. The method according to claim 1 , wherein the adjuvant is Al(OH) 3 or aluminum phosphate.