Whole-cell B.pertussis modulates tetanus response in mice immunized with DTPw vaccine

CASTRO MS; PIUDO L; LAVIGNE MV; DELUCHI S; ATZORI C; MATEO N; CALCAGNO ML; BRERO ML; MANGHI MA

Florida, USA

Congreso; Pharmaceutical Congress of the Americas; 2001

Recent studies indicate that particulate antigens enhance presentation of co-injected antigen by macrophages on the one hand, while reducing the availability of antigen to B lymphocytes on the other. This is significant, since macrophages have been associated with the induction of antigen-specific Th1 responses and B cells are believed to direct Th2 type responses. Purpose: Here we analyze the cellular immune response  to tetanus toxoid (TT) in Balb/c mice immunized with DTPw (particulate) ó DTPac (soluble) vaccines. Methods: Cytokine levels were measured by ELISA, T-cell proliferation by 3(H) thymidine incorporation. Results: IFNg, IL-5, IL-6 and IL-12 levels were measured in supernatants from spleen cell cultures stimulated with TT, TT/Bp or Bp. Stimuli with TT  induced IFNg  and IL-5 IFNg production by DTPw cells (Th1/Th2 response) and only IL-5 by DTPac (Th2 response). Stimulus with Bp only was recognized by DTPw cells which  proliferated and produced high IFNg  levels. IL-6 was produced only by spleen cells primed with DTPw. Probably, this result is on-line with the lack of  some whole-cell Bp component (LPS?) in DTPac vaccine formulation. IL-12 level measured in DTPw group was 3 times higher than the DTPac  (p<0.001). This observation is in accordance with the  IFNg levels measured when primed cells with DTPw were stimulated with TT ó Bp. Conclusion: Our findings indicate that the whole-cell Bp priming modifies the well-know Th2 tetanus response to a mixed Th1/Th2 type. On the other hand, the lacking of Bp recognition by DTPac primed cells is in accordance with the incomplete depuration of this pathogen reported in the mice respiratory infection model.