A monoclonal antibody identifies a protective C-protein alpha-antigen epitope in group B streptococci.
Group B streptococci (GBS) are the leading causes of neonatal sepsis and meningitis in the United States, with a high rate of fatality and serious morbidity despite appropriate therapy. The C-protein antigens of GBS appear to be important in immunity to experimental infection, yet these antigens remain incompletely characterized with respect to their number, structure, and function. None of these proteins has yet been purified to homogeneity. We have developed a novel method for extraction of surface proteins from the A909 (Ia/c) strain of GBS by using mutanolysin. Antibodies raised in rabbits against these partially purified proteins conferred passive protection to lethal GBS infection in mice challenged with a GBS strain expressing C proteins with a heterologous capsule type. In addition, mouse monoclonal antibodies were produced and identified by reactivity with the mutanolysin-extracted proteins. One of these monoclonal antibodies (4G8) identifies an epitope on the alpha-antigen of the GBS C proteins (identified by protease susceptibility and mouse protection). On sodium dodecyl sulfate-polyacrylamide gels, this epitope appears as a series of regularly spaced bands ranging in apparent molecular mass from 160,000 to 30,000 Da. The monoclonal antibody 4G8 induces opsonic killing of GBS and protects mice from lethal challenge with GBS. Thus, the 4G8 monoclonal antibody identifies a fully protective epitope on the C-protein alpha-antigen of GBS.
Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts.
L C
LC
Madoff
J L
JL
Michel
D L
DL
Kasper
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D010450:Endopeptidases / Q000302:isolation & purification; D000939:Epitopes / Q000032:analysis*; D007106:Immune Sera / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D013292:Streptococcus agalactiae / Q000276:immunology* / Q000472:pathogenicity; D014774:Virulence
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000939:Epitopes; D007106:Immune Sera; D010450:Endopeptidases; C021816:mutanolysin