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链球菌表面蛋白抗原合成肽对变形链球菌口腔定植的免疫原性及保护作用

Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen.

作者信息

Takahashi I, Okahashi N, Matsushita K, Tokuda M, Kanamoto T, Munekata E, Russell M W, Koga T

机构信息

Department of Dental Research, National Institute of Health, Tokyo, Japan.

出版信息

J Immunol. 1991 Jan 1;146(1):332-6.

PMID:1984447
Abstract

Streptococcus mutans is known to be a major causative organism of human dental caries. A surface protein Ag with a molecular mass of 190 kDa of S. mutans (PAc) is receiving attention as an anticaries vaccine. We have recently determined the complete nucleotide sequence of the gene for PAc. In this study, four peptides were synthesized on the basis of amino acid sequence of PAc. Among these peptides, PAc(301-319) corresponding to the alanine-rich repeating amino acid region was the most strongly bound by polyclonal murine anti-rPAc antibodies. The peptide partially inhibited the binding of polyclonal anti-rPAc antibodies to rPAc. The peptide induced the proliferation of T cells from BALB/c mice immunized with rPAc. Subcutaneous immunization with PAc(301-319) or rPAc emulsified in CFA/IFA induced high serum IgG responses to rPAc and PAc(301-319). In addition, serum IgG responses to a surface protein Ag with a molecular mass of 210 kDa of Streptococcus sobrinus were elicited in mice immunized by s.c. injection with PAc(301-319) or rPAc. Intranasal immunization with PAc(301-319) coupled to cholera toxin B subunit (CTB) or with rPAc and free CTB induced high serum IgG responses to rPAc. The immunization with PAc(301-319) coupled to CTB or rPAc and free CTB suppressed the colonization of murine teeth by S. mutans. These results suggest that intranasal immunization with the peptide or rPAc may be effective for the prevention of dental caries.

摘要

变形链球菌是已知的人类龋齿的主要致病微生物。变形链球菌一种分子量为190 kDa的表面蛋白抗原(PAc)作为一种抗龋齿疫苗正受到关注。我们最近确定了PAc基因的完整核苷酸序列。在本研究中,根据PAc的氨基酸序列合成了四种肽。在这些肽中,对应于富含丙氨酸的重复氨基酸区域的PAc(301 - 319)与多克隆鼠抗rPAc抗体的结合最强。该肽部分抑制多克隆抗rPAc抗体与rPAc的结合。该肽诱导用rPAc免疫的BALB/c小鼠的T细胞增殖。用PAc(301 - 319)或乳化于CFA/IFA中的rPAc进行皮下免疫诱导了对rPAc和PAc(301 - 319)的高血清IgG反应。此外,通过皮下注射PAc(301 - 319)或rPAc免疫的小鼠中引发了对远缘链球菌一种分子量为210 kDa的表面蛋白抗原的血清IgG反应。用与霍乱毒素B亚基(CTB)偶联的PAc(301 - 319)或用rPAc和游离CTB进行鼻内免疫诱导了对rPAc的高血清IgG反应。用与CTB偶联的PAc(301 - 319)或rPAc和游离CTB进行免疫抑制了变形链球菌在小鼠牙齿上的定植。这些结果表明,用该肽或rPAc进行鼻内免疫可能对预防龋齿有效。

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