RETRACTED ARTICLE: Self-assembling anticaries mucosal vaccine containing ferritin cage nanostructure and glucan-binding region ofS. mutansglucosyltransferase effectively prevents caries formation in rodents

Abstract

Anticaries protein vaccines that induce a mucosal immune response are not effective. Therefore, development of effective and convenient anticaries vaccines is a priority of dental research. Here we generated self-assembling nanoparticles by linking the glucan-binding region of Streptococcus mutans glucosyltransferase (GLU) to the N-terminal domain of ferritin to determine whether these novel nanoparticles enhanced the immunogenicity of an anticaries protein vaccine against GLU in rodents. We constructed the expression plasmid pET28a-GLU-FTH and purified the proteins from bacteria using size-exclusion chromatography. BALB/c mice were used to evaluate the ability of GLU-ferritin (GLU-FTH) nanoparticles to induce GLU-specific mucosal and systemic responses. The protective efficiency of GLU-FTH nanoparticles was compared with that of GLU alone or a mixture of GLU and poly(I:C) after administering an intranasal infusion to Wistar rats. The phagocytosis and maturation of dendritic cells (DCs) exposed in vitro to the nanoparticles were assessed using flow cytometry. The GLU-FTH nanoparticle vaccine elicited significantly higher levels of GLU-specific antibodies compared with GLU or a mixture of GLU and poly(I:C). Immunization with GLU-FTH achieved lower caries scores compared with those of the other vaccines. Administration of GLU-FTH nanoparticles enhanced phagocytosis by DCs and their maturation. Thus, self-assembling GLU-FTH is a highly effective anticaries mucosal vaccine that enhanced antibody production and inhibited S. mutans infection in rodents.

Glycan recognition at the saliva – oral microbiome interface

“…Rodent studies have demonstrated that vaccines containing the Gtf or GbpB protein result in detectable levels of specific salivary IgA and serum IgG. Importantly, this immunization results in significantly less total caries [244–246]. It is believed that IgA and IgG present in saliva bind to Gtf or GbpB, thereby preventing bacterial adhesion to extracellular bacterial polysaccharides in dental plaque and leading to agglutination and clearance of the S. mutans organisms [246].…”

The Combinations Chitosan-Pam 3 CSK 4 and Chitosan-Monophosphoryl Lipid A: Promising Immune-Enhancing Adjuvants for Anticaries Vaccine PAc

“…On week 0, seven groups of six animals each were immunized via buccal mucosa injection with 50 g of PAc, PAc plus 32 g of chitosan, PAc plus 15 g of MPL, PAc plus 25 g of Pam 3 CSK 4 , PAc-chitosan-Pam 3 CSK 4 , PAc-chitosan-MPL, or PBS and boosted on week 2. Cariogenic bacterial levels were tested from weeks 1 to 5 (35). We used swabs presoaked in PBS to collect S. mutans on fissures and smooth surfaces of molar teeth and transferred the samples to 500 l of PBS by vortexing.…”

Dental caries vaccine: are we there yet?

“…mutans colonization reduced. Perhaps, with new technology such as nano delivery systems and increasing knowledge, these vaccines can be improved further and taken into human clinical trials (Li et al ; Cao et al ).…”

“…Research has also been conducted to improve the efficacy and the delivery of caries vaccines using nanotechnology. Cao et al () successfully generated self‐assembling nanoparticles by linking the GB region of glucosyltransferase (GLU) to the N‐terminal domain of ferritin (GLU‐FTH) which significantly increased the level of GLU‐specific antibodies and produced lower caries scores compared to GLU in mice. Similar results were found by Li et al () using trimethyl chitosan nanoparticles.…”