Dinis Márcia, Tavares Delfina, Veiga-Malta Isabel, Fonseca António J M M, Andrade Elva Bonifácio, Trigo Gabriela, Ribeiro Adília, Videira Arnaldo, Cabrita António M Silvério, Ferreira Paula
Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), Porto, Portugal.
J Infect Dis. 2009 Jan 1;199(1):116-23. doi: 10.1086/594372.
Dental caries is among the more prevalent chronic human infections for which an effective human vaccine has not yet been achieved. Enolase from Streptococcus sobrinus has been identified as an immunomodulatory protein. In the present study, we used S. sobrinus recombinant enolase (rEnolase) as a target antigen and assessed its therapeutic effect in a rat model of dental caries. Wistar rats that were fed a cariogenic solid diet on day 18 after birth were orally infected with S. sobrinus on day 19 after birth and for 5 consecutive days thereafter. Five days after infection and, again, 3 weeks later, rEnolase plus alum adjuvant was delivered into the oral cavity of the rats. A sham-immunized group of rats was contemporarily treated with adjuvant alone. In the rEnolase-immunized rats, increased levels of salivary IgA and IgG antibodies specific for this recombinant protein were detected. A significant decrease in sulcal, proximal enamel, and dentin caries scores was observed in these animals, compared with sham-immunized control animals. No detectable histopathologic alterations were observed in all immunized animals. Furthermore, the antibodies produced against bacterial enolase did not react with human enolase. Overall, these results indicate that rEnolase could be a promising and safe candidate for testing in trials of vaccines against dental caries in humans.
龋齿是人类中较为普遍的慢性感染之一,目前尚未研发出有效的人类疫苗。远缘链球菌烯醇化酶已被确定为一种免疫调节蛋白。在本研究中,我们使用远缘链球菌重组烯醇化酶(rEnolase)作为靶抗原,并在大鼠龋齿模型中评估其治疗效果。出生后第18天开始喂食致龋固体饮食的Wistar大鼠,在出生后第19天口服感染远缘链球菌,并在此后连续5天感染。感染后5天以及3周后,将rEnolase加明矾佐剂注入大鼠口腔。一组假免疫大鼠同时仅用佐剂进行处理。在rEnolase免疫的大鼠中,检测到针对该重组蛋白的唾液IgA和IgG抗体水平升高。与假免疫对照动物相比,这些动物的龈沟、近中釉质和牙本质龋损评分显著降低。在所有免疫动物中均未观察到可检测到的组织病理学改变。此外,针对细菌烯醇化酶产生的抗体与人烯醇化酶不发生反应。总体而言,这些结果表明,rEnolase可能是一种有前景且安全的候选物,可用于人类龋齿疫苗试验的测试。