An optimized caries model of <i>Streptococcus mutans</i> in rats and its application for evaluating prophylactic vaccines

Dental caries is a prevalent oral disease that mainly results from <i>Streptococcus mutans</i>. Susceptibility to <i>S. mutans</i> decreased rapidly after weaning in a well-known rat model. However, owing to the lack of time to establish protective immunity ahead of challenge, the weaning rat model is suboptimal for assessing prophylactic vaccines against <i>S. mutans</i> infection. In this study, we found that, in adult rats, <i>S. mutans</i> cultured under air-restricted conditions showed dramatically increased colonization efficacy and accelerated development of dental caries compared with those cultured under air-unrestricted conditions. We propose that <i>S. mutans</i> cultured under air-restricted conditions can be used to develop an optimal caries model, especially for the evaluation of prophylactic efficacy against <i>S. mutans</i>. Therefore, we used the anti-caries vaccine, KFD2-rPAc, to reevaluate the protection against the challenge of <i>S. mutans</i>. In immunized rats, rPAc-specific protective antibodies were robustly elicited by KFD2-rPAc before the challenge. In addition to inhibiting the initial and long-term colonization of <i>S. mutans in vivo</i>, KFD2-rPAc immunization showed an 83% inhibitory efficacy against the development of caries, similar to that previously evaluated in a weaning rat model. These results demonstrate that culturing under air-restricted conditions can promote <i>S. mutans</i> infection in adult rats, thereby helping establish a rat infection model to evaluate the prophylactic efficacy of vaccines and anti-caries drugs.