Engineering the microflora to vaccinate the mucosa: serum immunoglobulin G responses 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 paediatric and immunocompromised populations by safe, non-invasive vectors, such as commensal lactobacilli, represents a crucial improvement to prevailing vaccination options. In this report, we describe the oral and nasal immunization of mice with vaccines constructed through an original system for heterologous gene expression in Lactobacillus in which the 50 000-molecular weight (MW) fragment C of tetanus toxin (TTFC) is expressed either as an intracellular or a surface-exposed protein. Our data indicate that L. plantarum is more effective in this respect than L. casei and that, under the experimental conditions investigated, delivery of TTFC expressed as an intracellular antigen is more effective than cell-surface expression. Immunization of mice with live recombinant lactobacilli induced significant levels of circulating TTFC-specific immunoglobulin G (IgG) following nasal or oral delivery of vaccine strains. In addition, following nasal delivery, secretory immunoglobulin A (sIgA) was induced in bronchoalveolar lavage fluids, as were antigen-specific antibody-secreting cells and antigen-specific T-cell activation in draining lymph nodes, substantiating their potential for safe mucosal delivery of paediatric vaccines.
TNO-Prevention and Health, Special Program Infectious Diseases, Zernikedreef, Leiden, The Netherlands.
D M
DM
Shaw
B
B
Gaerthé
R J
RJ
Leer
J G
JG
Van Der Stap
C
C
Smittenaar
M
M
Heijne Den Bak-Glashouwer
J E
JE
Thole
F J
FJ
Tielen
P H
PH
Pouwels
C E
CE
Havenith
D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007778:Lactobacillus / Q000235:genetics*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000276:immunology*; D013744:Tetanus Toxin / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology*
D007074:Immunoglobulin G; D010446:Peptide Fragments; D013744:Tetanus Toxin; D019444:Vaccines, DNA; C040635:tetanus toxin fragment C