Lactic Acid Bacteria Display System as antigen delivery vechicle for mucosal vaccine

Lactic acid bacteria (LAB) are widely used in food industries and even beneficial organisms. The potential of using Lactic acid bacteria for new applications such as an expression of heterologous proteins for diverse biotechnological area is currently under active study. Lactic acid bacteria have a variety of properties which make them attractive candidates for oral vaccination purposes, such as GRAS statue, adjuvant properties, cytokine secretion, induction of mucosal and systemic immune response and low intrinsic immunogenicity. We focused on development and optimization of surface display for heterologous proteins in Lactic acid bacteria. First, we have constructed a novel surface expression shuttle vector containing poly-γ-glutamic acid (γ-PGA) synthetase A (PgsA) protein as a display motif. The PgsA is a transmembrane anchor protein derived from γ-PGA synthetase complex (PgsBCA system) of Bacillus subtilis Chungkookjang and verified that PgsA could be used as a display motif by investigating the the surface expression of diverse antigens on Lactobacillus casei.

For the significant applications of Lactic acid bacteria display system, we studied L. casei displaying diverse viral antigens [Aninmal virues; TGE, PED, WSSV, AI, CPV and Human virues; HPV, SARS, HIV etc] in order to develop mucosal vaccine candidates for infectious viral diseases. Western blot, FACScan analysis, and immunofluorescence microscopy were performed to monitor the surface expression of each fusion protein on L. casei. The immunogenicity study of displayed antigens on the L. casei was performed using orally or intranasally immunized animals. We also developed L. casei expressing anti-tumor proteins [CEA, α-fetoprotein etc] or specific proteins [myostatin, β-amyloid etc] for the therapy of cancer, cachexia, or dementia. The study to investigate the prophylatic or therapeutic efficiency of Lactic acid bateria displaying target proteins is in progress using various animal models.

This Lactic acid bateria display system could be used for the expression of diverse heteologous proteins on Lactic acid bacteria which is applicable to the development of various mucosal vaccines and therapeutics.