Immunogenicity and protective efficacy of the alpha C protein of group B streptococci are inversely related to the number of repeats.
Infection by group B streptococci (GBS) is an important cause of bacterial disease in neonates. Alpha C protein is a protective cell surface-associated protein of GBS. This protein contains a repeat region flanked by N and C termini. Variable expression of tandem repeating units of alpha C proteins had been found among clinical isolates of GBS. We examined the effect of the number of repeats on the immunogenicity of the alpha C protein and its ability to elicit protection from GBS infection in a neonatal mouse model. Mice were immunized with purified alpha C proteins of constructs containing various numbers of repeats (n = 1, 2, 9, and 16) and the N- and C-terminal regions. Both the N-terminal and the repeat regions contain protective and opsonic epitopes. Antibody responses to the alpha C protein constructs with various numbers of repeats were tested with enzyme-linked immunosorbent assay plates coated with either native, nine-repeat alpha C protein or "repeatless" N-terminal antigen. An inverse relationship was found between the number of repeats and the immunogenicity of the alpha C protein; this effect was most pronounced on titers of antibody to the N-terminal region. An inverse relationship was also observed between the number of repeats and protective efficacy, i.e., mouse dams immunized with 5 microg of one- or nine-repeat alpha C protein transferred protective immunity to 65 or 11% of their pups, respectively (P < 0.0001). Thus, the presence of multiple repeats appears to lessen the antibody response to the complete alpha C protein, and especially the antibody response to its N-terminal region, and suggests a mechanism whereby repeat elements contribute to the evasion of host immunity.
Gravekamp
C
C
Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. Claudia.Gravekamp@channing.harvard.edu
Kasper
D L
DL
Michel
J L
JL
Kling
D E
DE
Carey
V
V
Madoff
L C
LC
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D012091:Repetitive Sequences, Nucleic Acid; D017421:Sequence Analysis; D013290:Streptococcal Infections / Q000276:immunology*; D013291:Streptococcus / Q000276:immunology*
D000954:Antigens, Surface; D001426:Bacterial Proteins; C077961:alpha C protein, group B streptococci