Induction of immune responses in mice after oral immunization with recombinant Lactobacillus casei strains expressing enterotoxigenic Escherichia coli F41 fimbrial protein.
In an effort to develop a safe and effective vaccine for the prevention of enterotoxigenic Escherichia coli (ETEC) F41 infections, we have developed a surface antigen display system using poly-gamma-glutamate synthetase A (PgsA) as an anchoring matrix. The recombinant fusion proteins comprised of PgsA and fimbrial protein of F41 were stably expressed in Lactobacillus casei 525. Surface localization of the fusion protein was verified by immunoblotting, immunofluorescence microscopy, and flow cytometry. Oral inoculation of recombinant L. casei 525 into specific-pathogen-free BALB/c mice resulted in significant mucosal immunoglobulin A (IgA) titers that remained elevated for >16 weeks. High levels of IgG responses in sera specific for F41 fimbriae were also induced, with prominent IgG1 titers as well as IgG2a and IgG2b titers. The helper T-cell (Th) response was Th2-cell dominant, as evidenced by increased mucosal and systemic interleukin-4-producing T cells and a concomitant elevation of serum IgG1 antibody responses. More than 80% of the mice were protected against challenge with a 2 x 10(4)-fold 50% lethal dose of standard-type F41 (C83919). The induced antibodies were important for eliciting a protective immune response against F41 infection. These results indicated that the use of recombinant L. casei 525 could be a valuable strategy for future vaccine development for ETEC.
Liu
Jian-Kui
JK
Heilongjiang August First Land Reclamation University, Daqing, China.
Hou
Xi-Lin
XL
Wei
Chun-Hua
CH
Yu
Li-Yun
LY
He
Xiao-Jie
XJ
Wang
Gui-Hua
GH
Lee
Jong-Soo
JS
Kim
Chul-Joong
CJ
D000284:Administration, Oral; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D054307:Enterotoxigenic Escherichia coli / Q000235:genetics / Q000276:immunology*; D004927:Escherichia coli Infections / Q000517:prevention & control*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000276:immunology*; D022361:Escherichia coli Vaccines / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D007070:Immunoglobulin A / Q000032:analysis; D007074:Immunoglobulin G / Q000097:blood; D007413:Intestinal Mucosa / Q000276:immunology; D007780:Lacticaseibacillus casei / Q000235:genetics*; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D016207:Cytokines; D029968:Escherichia coli Proteins; D022361:Escherichia coli Vaccines; C083561:F41 antigen, E coli; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins