Oral Therapeutic Vaccination withStreptococcus sobrinusRecombinant Enolase Confers Protection against Dental Caries in Rats

Abstract

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.

Streptococcus suisEnolase Functions as a Protective Antigen Displayed on the Bacterial Cell Surface

“…As we expected, we found that immunization with enolase confers protection against lethal SS2 infection in mice, prompting us to believe it could potentially be a candidate subunit vaccine against infection by the bacteria [18,19]. Very recently, a similar finding was reported regarding Streptococcus sobrinus, which indicated that oral therapeutic vaccination with recombinant enolase confers protection against dental caries in rats [30]. The findings that facilitated the design of a highly effective epitope vaccine prompted us to further address B cell epitopes and MHC II-restricted peptides for SS2 enolase (data not shown).…”

“…In fact, these enzymes play critical roles in bacterial colonization, persistence, and invasion of host tissue, in addition to their innate glycolytic and metabolic enzyme activities [29]. Enolase, an enzyme responsible for the dehydration of 2-phosphoglycerate (2-PGE) to phosphoenolpyruvate (PEP), was recognized recently as an immunodominant antigen involved in the virulence of Streptococcus species [24,27,30,31].…”

Bacterial Virulence in the Moonlight: Multitasking Bacterial Moonlighting Proteins Are Virulence Determinants in Infectious Disease

“…Thus, it can be concluded that cell surface enolase does contribute to bacterial virulence. Interestingly, in this context, it has been reported that the recombinant enolase from the oral bacterium Streptococcus sobrinus is an immunosuppressive protein (180) which can be used, if administered orally, to protect against dental caries in the rat (50). In contrast, with Paenibacillus larvae, the Grampositive causative agent of American foulbrood (AFB), which affects the larvae of the honeybee, Apis mellifera, the enolase is a secreted highly immunogenic protein which is thought to play a role in the virulence of this bacterium (9).…”

Effects of Streptococcus mutans on Dendritic Cell Activation and Function

“…Whether these antibodies are protective or simply a response to colonization is difficult to elucidate, since interpretation of human studies is confounded by study variation and the numerous factors influencing caries development (reviewed in Smith and Mattos-Graner, 2008). Nonetheless, vaccine studies in animal models of dental caries demonstrate the potential for manipulating the immune response to generate specific antibodies, which may reduce colonization and subsequent caries in these animals (Culshaw et al, 2007;Dinis et al, 2009Dinis et al, , 2011. The mechanisms driving these immune responses are unknown, and although the potential exists for individuals to raise antibodies to Streptococcus mutans, to date, this has proved challenging to manipulate effectively.…”