Specificity and protective activity of murine monoclonal antibodies directed against the capsular polysaccharide of type III group B streptococci.
We have obtained 41 monoclonal antibodies directed against type III group B streptococci by immunizing Balb/c mice with formalin-killed bacteria. All of these antibodies reacted with purified type-specific carbohydrate by enzyme-linked immunosorbent assay and immunoprecipitation tests. The epitope recognized by all of these antibodies was associated with terminal sialic acid residues, as indicated by abrogation of immune reactions by treatment of the type-specific carbohydrate with neuraminidase. Two purified monoclonal antibodies (the IgM P9D8 and the IgG3 P4F12) were further characterized for their protective activity in a neonatal rat model of infection. P9D8 and P4F12 antibodies were significantly protective when administered in a dose of 0.5 and 2.5 mg/kg, respectively, at the same time as 3 x 10(5) colony forming units of type III streptococci. Protection was still observed when the antibodies were given up to 9 h after challenge. No protection was afforded against infections with type Ia/c and II streptococci. Similarly, both antibodies effectively opsonized type III, but not Ia, Ib or II bacteria, in an in vitro assay. These and similar, previously described, monoclonal antibodies may be useful, possibly after "humanization" by genetic engineering, for the therapy of neonatal group B streptococcal infections.
Istituto di Microbiologia, Facoltà di Medicina e Chirurgia, Università degli Studi di Messina, Italy.
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Teti
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Calapai
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Calogero
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Tomasello
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Mancuso
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Galli
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Riggio
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology* / Q000302:isolation & purification; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000276:immunology* / Q000302:isolation & purification; D001427:Bacterial Toxins / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D007158:Immunologic Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019158:N-Acetylneuraminic Acid; D009439:Neuraminidase; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D051381:Rats; D011919:Rats, Inbred Strains; D012794:Sialic Acids / Q000276:immunology; D013290:Streptococcal Infections / Q000517:prevention & control*; D013292:Streptococcus agalactiae / Q000276:immunology*
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D000939:Epitopes; D011135:Polysaccharides, Bacterial; D012794:Sialic Acids; C032263:streptococcal polysaccharide type III group B; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid