GeMI-Vax as a multi-life stage malaria vaccine

New methods for simultaneous presentation and immune stimulation of malarial antigens are needed in order to rapidly progress promising antigens into efficacious vaccines. Platforms that present antigen to the immune system in a particulate manner that mimics the structure of a natural pathogen may improve the effectiveness of a vaccine. Many forms of particles exist for vaccine presentation including adsorption of recombinant vaccine antigen onto adjuvant material, and formation of virus-like particles. In this proposal we demonstrate that Gene-Mediated Inactivated Vaccines (GeMI-Vax) made from Gram-negative bacteria serve as "viral-like" particles for antigen delivery and contain intrinsic immunostimulatory capabilities. Specifically, the circumsporozoite protein (CSP) antigen from Plasmodium berghii was expressed on the surface and in the periplasmic space of Eschericia coli. GeMI-Vax-CSP vaccines were demonstrated to induce CSP-specific immune responses and sterile protection in a live P. berghii mouse model of malaria challenge. These results demonstrate that GeMI-Vax can serve as vaccine particles and immunostimulants for the induction of protective immune responses to CSP and likely to other malaria vaccine antigens. Thus, the objective of this Phase I proposal is to develop GeMI-Vax with various malarial antigens into a multi-life stage vaccine product for human use.