Ma J K, Hunjan M, Smith R, Kelly C, Lehner T
Department of Immunology, United Medical and Dental School, Guy's Hospital, London, United Kingdom.
Infect Immun. 1990 Oct;58(10):3407-14. doi: 10.1128/iai.58.10.3407-3414.1990.
Local oral passive immunization with Streptococcus mutans-specific monoclonal antibody (MAb) (Guy's 13) prevented recolonization by indigenous S. mutans in human volunteers who had first been treated with a conventional antibacterial agent (chlorhexidine). The F(ab')2 fragment of the MAb was as protective as the intact immunoglobulin G, but the Fab fragment of the molecule failed to prevent recolonization of S. mutans. In subjects receiving the MAb Fab fragment, S. mutans levels in dental plaque and saliva reappeared at a similar rate to that found in sham-immunized subjects who received either saline or a nonprotective MAb. In vitro, MAb had no bacteriostatic or bacteriocidal effect on S. mutans. However, S. mutans grown in the presence of either intact immunoglobulin G MAb or the F(ab')2 fragment formed very long chains, which resulted in clumping of the cells. S. mutans grown with either saline or the MAb Fab fragment formed significantly shorter chains, more characteristic of streptococcal growth in liquid media. The results suggest that the two binding sites of the MAb molecule may be an essential feature for preventing streptococcal colonization but that the ability to bind to phagocytes and activate complement which resides in the Fc fragment is not essential. Protection against colonization by S. mutans lasting up to 2 years was observed in immunized subjects, although MAb was applied over a period of only 3 weeks. Furthermore, functional MAb was detected up to 3 days following application of MAb to the teeth. The long-term protection could not be accounted for by a persistence of MAb on the tooth surface, and we have suggested that it may be due to a shift in the balance of the oral flora which discouraged recolonization by S. mutans. However, examination of the proportions of Streptococcus sanguis and veillonella species in the recolonization experiments failed to reveal a significant change in the proportions of either organism, which returned to approximately the preexperimental levels in both the immunized and control groups. These findings confirm the in vivo functional specificity of the MAb to S. mutans but are not consistent with the suggestion that S. sanguis or veillonella take over the niche vacated by S. mutans, unless the shift in the proportion of these organisms cannot be detected by the method used.
用变形链球菌特异性单克隆抗体（MAb）（盖伊氏13）进行局部口腔被动免疫，可防止曾先用常规抗菌剂（洗必泰）治疗的人类志愿者口腔内的变形链球菌再次定殖。MAb的F(ab')2片段与完整的免疫球蛋白G具有同样的保护作用，但该分子的Fab片段无法防止变形链球菌再次定殖。在接受MAb Fab片段的受试者中，牙菌斑和唾液中的变形链球菌水平重新出现的速度，与接受生理盐水或无保护作用的MAb的假免疫受试者相似。在体外，MAb对变形链球菌没有抑菌或杀菌作用。然而，在完整免疫球蛋白G MAb或F(ab')2片段存在的情况下生长的变形链球菌形成了非常长的链，导致细胞聚集。在生理盐水或MAb Fab片段存在的情况下生长的变形链球菌形成的链明显更短，更具液体培养基中链球菌生长的特征。结果表明，MAb分子的两个结合位点可能是防止链球菌定殖的关键特征，但与吞噬细胞结合并激活Fc片段中补体的能力并非必不可少。在免疫受试者中观察到对变形链球菌定殖的保护作用持续长达2年，尽管MAb仅应用了3周。此外，在将MAb应用于牙齿后长达3天仍能检测到有功能的MAb。长期保护作用无法用MAb在牙齿表面的持续存在来解释，我们认为这可能是由于口腔菌群平衡的改变，抑制了变形链球菌的再次定殖。然而，在再定殖实验中检查血链球菌和韦荣氏菌属的比例，未能发现这两种菌的比例有显著变化，在免疫组和对照组中它们都恢复到了接近实验前的水平。这些发现证实了MAb在体内对变形链球菌的功能特异性，但与血链球菌或韦荣氏菌占据变形链球菌空出的生态位的观点不一致，除非用所使用的方法无法检测到这些菌比例的变化。
