Immunogenicity and protective immunity induced by synthetic peptides associated with a catalytic subdomain of mutans group streptococcal glucosyltransferase.
We examined the immunogenicity and induction of protective immunity of two 19-mer sequences (GGY and AND) which overlapped a highly conserved region which has recently been implicated in the enzymatic activity of glucosyltransferases (GTFs) of the mutans group streptococci. These peptides were synthesized as eight-branched constructs on a lysine core. Serum immunoglobulin G (IgG) antibody, induced by subcutaneous (s.c. [salivary gland vicinity]) injection with these peptide constructs, reacted with the inciting antigen, with mutans streptococcal GTFs, and with a 21-mer peptide (CAT) containing an aspartate previously shown to covalently bind sucrose. Several of these antisera also inhibited the ability of Streptococcus sobrinus GTF to synthesize insoluble glucan. Significant levels of salivary IgA antibody were also induced by GGY and AND peptide constructs after s.c. injection. The effect of immunization with the GGY and AND peptide constructs on the cariogenicity of Streptococcus mutans was studied in three experiments by immunization of weanling Sprague-Dawley rats, twice at 7- to 14-day intervals with peptides, S. sobrinus GTF, or phosphate-buffered saline. All rats were then orally infected with S. mutans SJ. After 63-day infection periods, the GGY and AND-injected groups had significant dental caries reductions compared with sham-injected groups in most experiments. These studies support the existence of an additional catalytic subdomain within the sequence defined by the GGY and AND peptides. Furthermore, the epitopes defined in these sequences have significant immunogenicity, can induce immune responses which interfere with GTF-mediated glucan synthesis in vitro, and can protect rats from experimental dental caries.
Smith
D J
DJ
Department of Immunology, Forsyth Dental Center, Boston, Massachusetts 02115, USA.
Shoushtari
B
B
Heschel
R L
RL
King
W F
WF
Taubman
M A
MA
D000595:Amino Acid Sequence; D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D005964:Glucosyltransferases / Q000276:immunology*; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013291:Streptococcus / Q000201:enzymology / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*
D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D014614:Vaccines, Synthetic; D005964:Glucosyltransferases