A Caries Vaccine: Use of a Salmonella Vector, Recombinant Streptococcus mutans Antigen and Adjuvants

Objectives:Dental Caries is an infectious disease in which the principle etiologic agent is the mutans streptococci, especially Streptococcus mutans. Since this disease involves the colonization and subsequent destruction of tooth surfaces, attention over the years has been directed towards the development of novel vaccination strategies that lead to the induction of salivary IgA antibodies, which are considered a first line of defense of oral surfaces. Methods:Recently our interests have been directed to establish the effectiveness of recombinant S. mutans proteins for the development of a caries vaccine. We have concentrated on the saliva-binding region (SBR) of the adhesin antigen I/I and on the glucan-binding region (GLU) of glucosyltransferase. We have shown that SBR and GLU and especially SBR-GLU are effective in inducing mucosal responses that protect against S.mutans infection. To potentiate responses to our antigens, we have also used adjuvants and a Salmonella vector. However, to optimize a vaccine, it is important to understand the cellular mechanisms involved in host responses to each component. Therefore, we are assessing the role of the co-stimulatory molecules, Toll-like receptors (TLRs), and cell-signaling pathways involved in host responses to our candidate vaccines. Results:We have recently shown a difference in the involvement of CD80 and CD86 in host response to Salmonella compared to the expressed SBR. We have also shown a difference in the adjuvant activity of two flagellin components of Salmonella that act via TLR5. Conclusions:These results should help in the development of an optimum human vaccine against dental caries. Supported by USPHS grants DE 09081, DE 08182, DE 14215 and AI 56460.