Functional Exploration of the Immune Response Using the B-Subunit of Cholera Toxin Administered by Mucosal Way in Healthy Adult Volunteer: Potential Role in Development of Vaccine Processes

It is a biomedical research without direct individual benefit, exploring and comparing the mucosal immune response after oral, nasal and sublingual administration of B-subunit of non-toxic cholera toxin (CTB) in healthy adult volunteers.

开始日期2006-04-01

申办/合作机构

Centre Hospitalier Universitaire de Nice

100 项与 B-subunit of non-toxic cholera toxin vaccine(Centre Hospitalier Universitaire de Nice) 相关的临床结果

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100 项与 B-subunit of non-toxic cholera toxin vaccine(Centre Hospitalier Universitaire de Nice) 相关的转化医学

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100 项与 B-subunit of non-toxic cholera toxin vaccine(Centre Hospitalier Universitaire de Nice) 相关的专利（医药）

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项与 B-subunit of non-toxic cholera toxin vaccine(Centre Hospitalier Universitaire de Nice) 相关的文献（医药）

2024-12-01·Molecular Biotechnology

An In Silico Multi-epitopes Vaccine Ensemble and Characterization Against Nosocomial Proteus penneri

Article

作者: Rehman, Bushra ; Ahmad, Sajjad ; Irfan, Muhammad ; Almanaa, Taghreed N ; Khan, Saifullah ; Hassan, Muhammad ; Naz, Tahira ; Muhammad, Riaz ; Sanami, Samira ; Ullah, Asad ; Waheed, Yasir ; Ul Haq, Mehboob

Proteus penneri (P. penneri) is a bacillus-shaped, gram-negative, facultative anaerobe bacterium that is primarily an invasive pathogen and the etiological agent of several hospital-associated infections. P. penneri strains are naturally resistant to macrolides, amoxicillin, oxacillin, penicillin G, and cephalosporins; in addition, no vaccines are available against these strains. This warrants efforts to propose a theoretical based multi-epitope vaccine construct to prevent pathogen infections. In this research, reverse vaccinology bioinformatics and immunoinformatics approaches were adopted for vaccine target identification and construction of a multi-epitope vaccine. In the first phase, a core proteome dataset of the targeted pathogen was obtained using the NCBI database and subjected to bacterial pan-genome analysis using bacterial pan-genome analysis (BPGA) to predict core protein sequences which were then used to find good vaccine target candidates. This identified two proteins, Hcp family type VI secretion system effector and superoxide dismutase family protein, as promising vaccine targets. Afterward using the IEDB database, different B-cell and T-cell epitopes were predicted. A set of four epitopes "KGSVNVQDRE, NTGKLTGTR, IIHSDSWNER, and KDGKPVPALK" were chosen for the development of a multi-epitope vaccine construct. A 183 amino acid long vaccine design was built along with "EAAAK" and "GPGPG" linkers and a cholera toxin B-subunit adjuvant. The designed vaccine model comprised immunodominant, non-toxic, non-allergenic, and physicochemical stable epitopes. The model vaccine was docked with MHC-I, MHC-II, and TLR-4 immune cell receptors using the Cluspro2.0 web server. The binding energy score of the vaccine was - 654.7 kcal/mol for MHC-I, - 738.4 kcal/mol for MHC-II, and - 695.0 kcal/mol for TLR-4. A molecular dynamic simulation was done using AMBER v20 package for dynamic behavior in nanoseconds. Additionally, MM-PBSA binding free energy analysis was done to test intermolecular binding interactions between docked molecules. The MM-GBSA net binding energy score was - 148.00 kcal/mol, - 118.00 kcal/mol, and - 127.00 kcal/mol for vaccine with TLR-4, MHC-I, and MHC-II, respectively. Overall, these in silico-based predictions indicated that the vaccine is highly promising in terms of developing protective immunity against P. penneri. However, additional experimental validation is required to unveil the real immune response to the designed vaccine.

2024-05-01·Plant Biotechnology Journal

Marked enhancement of the immunogenicity of plant‐expressed IgG‐Fc fusion proteins by inclusion of cholera toxin non‐toxic B subunit within the single polypeptide

Article

作者: Jang, Yong-Suk ; Kwon, Tae-Ho ; Vergara, Emil ; Reljic, Rajko ; Ma, Julian K C ; Kim, Mi-Young ; Tran, Andy ; Paul, Matthew John

SummaryImmunoglobulin G (IgG)‐based fusion proteins have been widely exploited as a potential vaccine delivery platform but in the absence of exogenous adjuvants, the lack of robust immunity remains an obstacle. Here, we report on a key modification that overcomes that obstacle. Thus, we constructed an IgG‐Fc vaccine platform for dengue, termed D‐PCF, which in addition to a dengue antigen incorporates the cholera toxin non‐toxic B subunit (CTB) as a molecular adjuvant, with all three proteins expressed as a single polypeptide. Following expression in Nicotiana benthamiana plants, the D‐PCF assembled as polymeric structures of similar size to human IgM, a process driven by the pentamerization of CTB. A marked improvement of functional properties in vitro and immunogenicity in vivo over a previous iteration of the Fc‐fusion protein without CTB [1] was demonstrated. These include enhanced antigen presenting cell binding, internalization and activation, complement activation, epithelial cell interactions and ganglioside binding, as well as more efficient polymerization within the expression host. Following immunization of mice with D‐PCF by a combination of systemic and mucosal (intranasal) routes, we observed robust systemic and mucosal immune responses, as well as systemic T cell responses, significantly higher than those induced by a related Fc‐fusion protein but without CTB. The induced antibodies could bind to the domain III of the dengue virus envelope protein from all four dengue serotypes. Finally, we also demonstrated feasibility of aerosolization of D‐PCF as a prerequisite for vaccine delivery by the respiratory route.

2023-07-19·BioImpacts

Design and computational analysis of an effective multi-epitope vaccine candidate using subunit B of cholera toxin as a build-in adjuvant against urinary tract infections

Article

作者: Asadi Karam, Mohammad Reza ; Habibi, Mehri ; Ehsani, Parasoo ; Rezaei, Maryam ; Bouzari, Saeid

Introduction: Urinary tract infection (UTI) is one of the most common infections, usually caused by uropathogenic Escherichia coli (UPEC). However, antibiotics are a usual treatment for UTIs; because of increasing antibiotic-resistant strains, vaccination can be beneficial in controlling UTIs. Using immunoinformatics techniques is an effective and rapid way for vaccine development. Methods: Three conserved protective antigens (FdeC, Hma, and UpaB) were selected to develop a novel multi-epitope vaccine consisting of subunit B of cholera toxin (CTB) as a mucosal build-in adjuvant to enhance the immune responses. Epitopes-predicted B and T cells and suitable linkers were used to separate them and effectively increase the vaccine's immunogenicity. The vaccine protein's primary, secondary, and tertiary structures were evaluated, and the best 3D model was selected. Since CTB is the TLR2 ligand, molecular docking was made between the vaccine protein and TLR2. Molecular dynamic (MD) simulation was employed to evaluate the stability of the vaccine protein-TLR2 complex. The vaccine construct was subjected to in silico cloning. Results: The designed vaccine protein has multiple properties in the analysis. The HADDOCK outcomes show an excellent interaction between vaccine protein and TLR2. The MD results confirm the stability of the vaccine protein- TLR2 complex during the simulation. In silico cloning verified the expression efficiency of our vaccine protein. Conclusion: The results of this study suggest that our designed vaccine protein could be a promising vaccine candidate against UTI, but further in vitro and in vivo studies are needed.

100 项与 B-subunit of non-toxic cholera toxin vaccine(Centre Hospitalier Universitaire de Nice) 相关的药物交易

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