The pH-responsive zeolitic imidazolate framework nanoparticle as a promising immune-enhancing adjuvant for anti-caries vaccine

Yu, You-Bo; Liu, Ying; Li, Sha; Yang, Xiao-Yan; Guo, Zhong

doi:10.1016/j.jdent.2023.104413

Cited by 3 publications

(1 citation statement)

References 36 publications

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“…Over the past decade, several experiments have been conducted to develop vaccines for preventing and treating dental caries with immunotherapy [13,14]. Caries vaccination has emerged as a highly promising method for preventing dental caries, presenting the advantage of offering long-term defense against this dental condition [15].…”

Section: Introductionmentioning

confidence: 99%

Immunoinformatics-Driven Multiepitope Vaccine Targeting Streptococcus mutans for Dental Caries Prevention

Pangabam,

Naorem,

Teli

et al. 2023

Preprint

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Streptococcus mutans is a major causative agent of dental caries and associated infections, posing significant challenges in oral healthcare. To develop an effective vaccine against S. mutans, we employed an immunoinformatics approach to identify potential vaccine candidates and design a multiepitope vaccine. The genomes of S. mutans were analyzed, and five core-proteins (PBP2X, PBP2b, MurG, ATP-F, and AGPAT) were selected as vaccine candidates based on antigenicity and conservation. Linear B-cell and T-cell epitopes were predicted from these proteins, and four B-cell epitopes and ten T-cell epitopes were chosen for vaccine construction. The multiepitope vaccine comprised 10 CTL epitopes, 5 HTL epitopes, and 5 linear B-cell epitopes linked with appropriate linkers. A 50S ribosomal L7/L12 protein was used as an adjuvant at the N-terminal. The final vaccine construct exhibited high antigenicity, solubility, and stability. The tertiary structure was modeled using AlphaFold v.2 and refined with GalaxyRefine. The refined 3D model had improved quality scores and structural stability. Molecular docking simulations revealed strong interactions between the vaccine and Toll-Like Receptors (TLRs). In silico immune simulation demonstrated the vaccine's ability to trigger both humoral and cell-mediated immune responses. The vaccine design strategy presented here provides a promising platform for developing a potential multiepitope vaccine against S. mutans, offering a novel approach to combat dental caries and associated infections. Further, experimental evaluations should be performed to validate its efficacy and safety as a potential vaccine candidate for dental health.

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Section: Introductionmentioning

confidence: 99%

Immunoinformatics-Driven Multiepitope Vaccine Targeting Streptococcus mutans for Dental Caries Prevention

Pangabam,

Naorem,

Teli

et al. 2023

Preprint

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Oral Administration as an Alternative Route for Sustained-Release Hydrogel-Encapsulated Anti-Caries Gene Vaccine (Preprint)

Li,

Guan,

et al. 2024

Preprint

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UNSTRUCTURED Streptococcus mutans (S. mutans) is the primary pathogenic bacterium causing dental caries, and the protein antigen (SpaP) of its P region and the glucan-binding protein (Gbp) with glucan-binding domain (GBD) exhibit promising immunogenicity. They have been separately utilized in the development of anti-caries vaccines, but their effectiveness needs enhancement. To improve the immune response and address challenges in the acidic gastrointestinal environment, such as antigen degradation, mucosal barriers, inefficient cellular absorption by immune cells, and rapid enzymatic degradation of vaccines, this study aims to create an innovative anti-caries vaccine using a temperature-sensitive sustained-release hydrogel as a carrier and evaluate the vaccine's immune response both in vitro and in vivo. In this study, we successfully connected the antigens of the P region of the recombinant protein SpaP from S. mutans and the glucan-binding domain (GBD) of GbpA. Using a sustained-release temperature-sensitive hydrogel, PLGA-PEG-PLGA, as a carrier, the anti-caries vaccine pVAX1-SPG was prepared. Initially, the sustained-release effect of the anti-caries vaccine was observed in vitro. Subsequently, rabbits were immunized orally and by injection to evaluate the vaccine's immune response and conduct general safety testing. pVAX1-SPG improved vaccine release in vitro, maintaining efficacy for a longer duration. In rabbits, it induced an elevation of SpaP-specific serum IgG and saliva IgA antibodies. Moreover, orally administered pVAX1-SPG induced stronger SpaP-specific serum IgG and saliva IgA antibodies than the injection route. No abnormalities were detected in various safety indicators. The temperature-sensitive sustained-release hydrogel-encapsulated pVAX1-SPG anti-caries gene vaccine can elicit a significantly effective and long-term immune response. The oral route proves to be a more readily accepted and safer alternative, holding enormous potential in the prevention and treatment of dental caries.

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Immunoinformatics Design of a Multiepitope Vaccine (MEV) Targeting Streptococcus mutans: A Novel Computational Approach

Naorem,

Pangabam,

Bora

et al. 2024

Pathogens

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Dental caries, a persistent oral health challenge primarily linked to Streptococcus mutans, extends its implications beyond dental decay, affecting over 4 billion individuals globally. Despite its historical association with childhood, dental caries often persists into adulthood with prevalence rates ranging from 60 to 90% in children and 26 to 85% in adults. Currently, there is a dearth of multiepitope vaccines (MEVs) specifically designed to combat S. mutans. To address this gap, we employed an immunoinformatics approach for MEV design, identifying five promising vaccine candidates (PBP2X, PBP2b, MurG, ATP-F, and AGPAT) based on antigenicity and conservation using several tools including CELLO v.2.5, Vaxign, v2.0, ANTIGENpro, and AllerTop v2.0 tools. Subsequent identification of linear B-cell and T-cell epitopes by SVMTrip and NetCTL/NetMHC II tools, respectively, guided the construction of a MEV comprising 10 Cytotoxic T Lymphocyte (CTL) epitopes, 5 Helper T Lymphocyte (HTL) epitopes, and 5 linear B-cell epitopes, interconnected by suitable linkers. The resultant MEV demonstrated high antigenicity, solubility, and structural stability. In silico immune simulations showcased the MEV’s potential to elicit robust humoral and cell-mediated immune responses. Molecular docking studies revealed strong interactions between the MEV construct and Toll-Like Receptors (TLRs) and Major Histocompatibility Complex (MHC) molecules. Remarkably, the MEV–TLR-4 complexes exhibited a low energy score, high binding affinity, and a low dissociation constant. The Molecular Dynamic (MD) simulation analysis suggested that MEV–TLR-4 complexes had the highest stability and minimal conformational changes indicating equilibrium within 40 nanosecond time frames. Comprehensive computational analyses strongly support the potential of the proposed MEV to combat dental caries and associated infections. The study’s computational assays yielded promising results, but further validation through in vitro and in vivo experiments is needed to assess its efficacy and safety.

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The pH-responsive zeolitic imidazolate framework nanoparticle as a promising immune-enhancing adjuvant for anti-caries vaccine

Cited by 3 publications

References 36 publications

Immunoinformatics-Driven Multiepitope Vaccine Targeting Streptococcus mutans for Dental Caries Prevention

Immunoinformatics-Driven Multiepitope Vaccine Targeting Streptococcus mutans for Dental Caries Prevention

Oral Administration as an Alternative Route for Sustained-Release Hydrogel-Encapsulated Anti-Caries Gene Vaccine (Preprint)

Immunoinformatics Design of a Multiepitope Vaccine (MEV) Targeting Streptococcus mutans: A Novel Computational Approach

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