Impact of intracellular location of and antigen display by intracellular bacteria: implications for vaccine development

Intracellular bacteria are primarily controlled by T-lymphocytes. The 'phag osomal' bacteria such as Salmonella enter ica and Mycobacterium bovis BCG r emain in the phagosome. These microbes primarily stimulate CD4 T-cells via antigen presentation through MHC class II molecules. In contrast, Listeria monocytogenes egresses from the phagosome into the cytoplasm by virtue of l isteriolysin. This 'cytoplasmic' pathogen is controlled by CD8 T-cells thro ugh MHC class I antigen presentation. Some bacterial pathogens such as Myco bacterium tuberculosis presumably remain in the phagosome but apparently 'p erforate' the phagosomal membrane and thus stimulate both CD4 and CD8 T-cel ls. We have constructed S. enterica and M. bovis BCG vaccine carriers which secrete listeriolysin. Such constructs are capable of introducing antigens into the MHC class II and MHC class I pathway, resulting in stimulation of both CD4 and CD8 T-cells. Moreover, we constructed S. enterica vaccines wh ich display one and the same listerial antigen in secreted and somatic form . Secreted antigen display was found to be superior to somatic antigen disp lay. Hence, we consider antigen secretion a major prerequisite of an effect ive vaccine against intracellular bacteria. (C) 1999 Elsevier Science B.V. All rights reserved.