Engineering the microflora to vaccinate the mucosa: serum immunoglobulin Gresponses and activated draining cervical lymph nodes following mucosal application of tetanus toxin fragment C-expressing lactobacilli

The delivery of antigens to mucosal-associated lymphoid tissues in paediatr ic and immunocompromised populations by safe, non-invasive vectors, such as commensal lactobacilli, represents a crucial improvement to prevailing vac cination options. In this report, we describe the oral and nasal immunizati on of mice with vaccines constructed through an original system for heterol ogous gene expression in Lactobacillus in which the 50 000-molecular weight (MW) fragment C of tetanus toxin (TTFC) is expressed either as an intracel lular or a surface-exposed protein. Our data indicate that L. plantarum is more effective in this respect than L. casei and that, under the experiment al conditions investigated, delivery of TTFC expressed as an intracellular antigen is more effective than cell-surface expression. Immunization of mic e with live recombinant lactobacilli induced significant levels of circulat ing TTFC-specific immunoglobulin G (IgG) following nasal or oral delivery o f vaccine strains. In addition, following nasal delivery, secretory immunog lobulin A (sIgA) was induced in bronchoalveolar lavage fluids, as were anti gen-specific antibody-secreting cells and antigen-specific T-cell activatio n in draining lymph nodes, substantiating their potential for safe mucosal delivery of paediatric vaccines.