Development of the passive immunization for prevention of dental caries using B cell epitopes of PAc.

点击翻译按钮获取中文摘要

A fimbria like surface protein (PAc) of Streptococcus mutans with a molecular mass of 190 kDa is one of the strong surface antigens of the Streptococcus and is involved in the initial attachment of this microorganism to the tooth surface. Thus, the protein antigen has been considered to be a good candidate for an anti-caries vaccine. Actually, it was successfully used as vaccine in the animal experiments. Passive immunization with monoclonal antibodies against the PAc was also reported to prevent dental caries in monkeys.In the present project, we constructed 7 truncated PAc fragments by using a DNA engineering and suggested that the alanine-rich repeating region (A-region) extended from the amino acid residues 219 to 464 of the PAc molecule is important in the binding of its surface protein to human salivary components and is possessed of the dominant antigenicity.We, therefore, synthesized 24 sequential overlapping 19 residues-peptides covering the entirety of A-region and determined T and B cell epitopes on the peptides by using a series of B10 congenic mice. Until now, at least 3 kinds of T cell epitopes and 3 kinds of B cell epitopes were identified. The results clearly indicate that murien immune responses to the PAc are restricted by the MHC class II gene haplotypes.Finally, to obtain the antigenic peptides for the passive immunization, the immunities of 16 synthetic peptides which contain the T and/or B cell epitopes were examined by immunization to the mice. The 5 of them, especially PAc(361-379) and PAc(391-409), can indue the production of antibodies against not only own peptide but also the native PAc molecule. These two antigenic peptides might be useful in the passive immunization for prevention of dental caries.