Intranasal immunization with recombinant group A streptococcal M protein fragment fused to the B subunit of Escherichia coli labile toxin protects mice against systemic challenge infections.
A fusion gene named LT-B-M5 was constructed encoding the entire B subunit of Escherichia coli labile toxin (LT-B), a 7 amino acid proline-rich linker, and 15 amino-terminal amino acids of type 5 streptococcal M protein. The purified LT-B-M5 was immunogenic in rabbits and evoked antibodies against a synthetic peptide copy of the amino-terminus of M5 (SM5[1-15]) and the native M5 protein and opsonic antibodies against type 5 streptococci. The hybrid protein retained the ganglioside-binding activity of LT-B and was tested in mice for its immunogenicity after local administration. Mice that were immunized intranasally with LT-B-M5 developed serum antibodies against SM5(1-15) and were significantly protected from death after intraperitoneal challenge infections with type 5 streptococci. The data show that protective systemic immune responses may be evoked after intranasal immunization with a fragment of M protein fused to LT-B.
Dale
J B
JB
Department of Veterans Affairs Medical Center, Memphis, TN 38104.
Chiang
E C
EC
D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D001483:Base Sequence; D002352:Carrier Proteins; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D013290:Streptococcal Infections / Q000517:prevention & control*; D013291:Streptococcus / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D002352:Carrier Proteins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005732:Gangliosides; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C014689:streptococcal M protein; C027538:heat-labile enterotoxin, E coli