Immunization with recombinant Streptococcus gordonii expressing tetanus toxin fragment C confers protection from lethal challenge in mice.
Tetanus toxin fragment C (TTFC) was expressed on the surface of the vaccine vector Streptococcus gordonii, a Gram-positive commensal bacterium of the human oral cavity. The immunogenicity of recombinant S. gordonii expressing TTFC was assayed in mice immunized by the parenteral and mucosal routes. High serum TTFC-specific IgG responses were induced in both BALB/c and C57BL/6 mice immunized subcutaneously. A total of 82% of vaccinated BALB/c mice were protected from the lethal challenge with 50 LD(50) of tetanus toxin (TT) and a direct correlation between the serum TTFC-specific IgG concentration and survival time of unprotected animals was observed. Intranasal immunization of BALB/c mice was also effective in inducing TTFC-specific serum IgG and local IgA in lung washes. Furthermore, 38% of animals immunized intranasally were protected from the lethal challenge with 10 LD(50) of TT while all control animals died within 24 h. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after parenteral immunization in BALB/c mice (IgG1/IgG2a ratio congruent with6) while following mucosal immunization a mixed IgG1 and IgG2a pattern (IgG1/IgG2a ratio congruent with1) was observed. These data show that TTFC expressed on the surface of S. gordonii is immunogenic by the subcutaneous and mucosal routes and the immune response induced is capable of conferring protection from the lethal challenge with TT.
Laboratorio di Microbiologia Molecolare e Biotecnologia (LA.M.M.B.), Dipartimento di Biologia Molecolare, Sezione di Microbiologia, Università di Siena, Policlinico Le Scotte, Viale Bracci, 53100, Siena, Italy. medaglini@unisi.it
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D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D003017:Clostridium tetani / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D017931:DNA Primers / Q000235:genetics; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000145:classification; D007279:Injections, Subcutaneous; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D011995:Recombination, Genetic; D013291:Streptococcus / Q000235:genetics / Q000276:immunology*; D013742:Tetanus / Q000276:immunology / Q000517:prevention & control; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology* / Q000633:toxicity; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D017931:DNA Primers; D007074:Immunoglobulin G; D010446:Peptide Fragments; D013744:Tetanus Toxin; D014614:Vaccines, Synthetic