Redman T K, Harmon C C, Lallone R L, Michalek S M
Department of Microbiology, University of Alabama at Birmingham 35294, USA.
Infect Immun. 1995 May;63(5):2004-11. doi: 10.1128/iai.63.5.2004-2011.1995.
An attenuated, recombinant Salmonella typhimurium mutant, chi 4072(pYA2905), expressing the surface protein antigen A (SpaA) of Streptococcus sobrinus was investigated for its effectiveness in inducing protective immune responses against S. sobrinus-induced dental caries in an experimental caries model. Fischer rats were orally immunized with either 10(8) or 10(9) CFU of S. typhimurium chi 4072(pYA2905). Persistence of salmonellae in Peyer's patches and spleens and the induction of immune responses were determined. Maximum numbers of salmonellae were recovered from Peyer's patches of rats within the first week of immunization, with higher numbers recovered from rats given 10(9) CFU than from those given 10(8) CFU. Serum anti-Salmonella and anti-SpaA responses increased more rapidly in rats given 10(9) CFU than in rats given 10(8) CFU. The salivary antibody response to SpaA increased with time, but the response varied in the two groups. In a separate study, rats were orally immunized with the recombinant Salmonella mutant and then challenged with cariogenic S. sobrinus 6715. The levels of serum and salivary antibody and caries activity were assessed at the termination of the experiment. Higher levels of salivary immunoglobulin A antibody to SpaA and Salmonella carrier were detected in rats given 10(9) CFU than in those given 10(8) CFU, and these responses were higher than those in nonimmunized controls. Mandibular molars from immunized rats had lower numbers of recoverable streptococci and less extensive carious lesions than those from nonimmunized, control rats. These data indicate that oral immunization with an attenuated recombinant S. typhimurium expressing SpaA of S. sobrinus induces the production of antigen-specific mucosal antibody and confers protection against dental caries.
研究了一种表达远缘链球菌表面蛋白抗原A（SpaA）的减毒重组鼠伤寒沙门氏菌突变体chi 4072（pYA2905）在实验性龋齿模型中诱导针对远缘链球菌诱导的龋齿的保护性免疫反应的有效性。用10⁸或10⁹CFU的鼠伤寒沙门氏菌chi 4072（pYA2905）对Fischer大鼠进行口服免疫。测定沙门氏菌在派尔集合淋巴结和脾脏中的持久性以及免疫反应的诱导情况。在免疫的第一周内，从大鼠的派尔集合淋巴结中回收的沙门氏菌数量最多，给予10⁹CFU的大鼠回收的数量高于给予10⁸CFU的大鼠。给予10⁹CFU的大鼠血清抗沙门氏菌和抗SpaA反应比给予10⁸CFU的大鼠增加得更快。唾液对SpaA的抗体反应随时间增加，但两组反应有所不同。在另一项研究中，用重组沙门氏菌突变体对大鼠进行口服免疫，然后用致龋性远缘链球菌6715进行攻击。在实验结束时评估血清和唾液抗体水平以及龋齿活性。给予10⁹CFU 的大鼠中检测到的针对SpaA和沙门氏菌载体的唾液免疫球蛋白A抗体水平高于给予10⁸CFU的大鼠，并且这些反应高于未免疫对照中的反应。免疫大鼠的下颌磨牙中可恢复的链球菌数量较少，龋齿病变范围比未免疫的对照大鼠小。这些数据表明，用表达远缘链球菌SpaA的减毒重组鼠伤寒沙门氏菌进行口服免疫可诱导产生抗原特异性粘膜抗体并赋予抗龋齿保护作用。
