Bacterial vaccines deficient in the 2-c-methyl-d-erythritol-4-phosphate pathway and methods of preparation and use thereof

Abstract

The present invention relates to the preparation and use in primates of whole organismvaccines in which the MEP pathway is disrupted such that synthesis of HMBPP by the bacterial cells is substantially blocked. The data provided demonstrates that, when bacteria or other vaccine vectors that comprise an active MEP pathway are used in vaccine methods, the γδ T cell response dominates, potentially clearing the vaccine strain via γδ T cell-mediated killing of vector infected antigen presenting cells and reducing its utility as a stimulator of a productive adaptive immune response, specifically priming or boosting of CD4and CD8αβ T cell responses, specific for listerial-encoded antigens. By disrupting the MEP pathway, activation and expansion of γδ T cells is limited in the recipient primate, resulting in resulting in an increase in the magnitude and duration of inflammation and in the magnitude and duration of antigen presentation by the cellular vaccine.