Deimmunization of flagellin for repeated administration as a vaccine adjuvant

Khim, Koemchhoy; Bang, Yong Jun; Puth, Sao; Choi, Yoonjoo; Lee, Youn Suhk; Jeong, Kwangjoon; Lee, Shee Eun; Rhee, Joon Haeng

doi:10.1038/s41541-021-00379-4

Cited by 26 publications

(15 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have shown that the agellin is mainly composed of four domains: D0, D1, D2, and D3. The D0 and D1 domains located at the N/C ends of agellin are mainly composed of highly conserved α-helix and are the main area for exerting adjuvant functions; the D2 and D3 domains located in the HVR of agellin are highly variable, which mainly determines the antigenicity, and can reduce its antigenicity by deleting these domains (Liu, et al 2010;Khim, et al 2021). The results of structural prediction and analysis of FliC EcN are consistent with previous research.…”

Section: Discussionmentioning

confidence: 99%

Studies on the structure and stimulating effect on Caco-2 cells of flagellin and its truncated proteins of Escherichia coli Nissle 1917

Ou²,

Wen

et al. 2023

Preprint

View full text Add to dashboard Cite

This study aimed to investigate the structural characteristics and their effects on stimulating Caco-2 cells of Escherichia coli Nissle 1917 flagellin (FliCEcN) and its truncated proteins, FliC△174−506 (D2-D3 domain deleted) and FliC△274−406 (D3 domain deleted). The experiment predicted the tertiary structure of FliCEcN by Alphofold2, analyzed the structural characteristics of FliCEcN, FliC△174−506 and FliC△274−406 by surface-enhanced Raman spectroscopy (SERS) and circular dichroism (CD), and detected the secretion levels of IL-6 (interleukin-6), IL-10 (interleukin-10) and TNF-α (tumor necrosis factor-α) after FliCEcN, FliC△174−506 and FliC△274−406 stimulated Caco-2 cells for 6 and 12 h, respectively. The results showed that the NH3-ends and COOH-ends of FliCEcN were highly conserved, mainly composed of α-helix; the middle domains were highly variable, mainly composed of β-sheet and random coil. The Raman peaks of FliC△174−506 and FliC△274−406 generally maintained the main chain peaks of FliCEcN, while the side chain and amino acid peaks were absent to varying degrees. The composition of the secondary structure of FliC△174−506 and FliC△274−406 was altered. FliCEcN, FliC△174−506 and FliC△274−406 stimulated Caco-2 cells to secrete cytokines IL-10, IL-6 and TNF-α differently. The complete FliCEcN structure could stimulate more secretion of IL-10; the FliC△174−506 group had higher secretion of IL-6; and the FliC△274−406 group had higher secretion of TNF-α. In conclusion, deletion of different domains of the hypervariable region of FliCEcN affects its SERS and CD spectrum and stimulates Caco-2 cells to secrete cytokines.

show abstract

Section: Discussionmentioning

confidence: 99%

Studies on the structure and stimulating effect on Caco-2 cells of flagellin and its truncated proteins of Escherichia coli Nissle 1917

Ou²,

Wen

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…In the context of GPGPG linkers, these linkers can stimulate T-helper responses and the conformationally-dependent immunogenicity of helper and antibody epitopes 57 – 59 . In this study, to compensate for these vaccines' low immunogenicity, the D0/D1 domains of the flagellin protein from S. Typhimurium bacteria were utilized as an adjuvant to boost the effectiveness of immune system stimulation 60 . Also, The EAAAK linker was employed to connect the D0/D1 domains at the N-terminal region of the multi-epitope sequence .…”

Section: Discussionmentioning

confidence: 99%

A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach

Atapour

Vosough

Jafari

et al. 2022

Sci Rep

View full text Add to dashboard Cite

Malaria is a complex disease caused by parasites of the genus Plasmodium and is the leading cause of morbidity and mortality worldwide. The most severe form of malaria disease is caused by Plasmodium falciparum. Thus, a combination of different approaches is needed to control malaria. Resistance to first-line drugs and insecticides, on the other hand, makes the need for an effective vaccination more urgent than ever. Because erythrocyte parasites cause the most clinical symptoms, developing a vaccination for this stage of infection might be highly beneficial. In this research, we employed various bioinformatics methods to create an efficient multi-epitope vaccine that induces antibodies against the blood stage of malaria infection. For this purpose, we selected the malaria PfGARP protein as the target here. The B, HTL epitopes, and epitope conservation were predicted. The predicted epitopes (including 5 B and 5 HTL epitopes) were connected using suitable linkers, and the flagellin molecule was used as an adjuvant to improve its immunogenicity. The final construct vaccine with 414 amino acids long was designed. The vaccine's allergenicity, antigenicity, solubility, physicochemical characteristics, 2D and 3D structure modeling, molecular docking, molecular dynamics simulation, in silico cloning, and immunological simulation were tested. In silico immune simulation results showed significantly elevated IgG1 and IgM and T helper cells, INF γ, IL 2, and B-cell populations after the injection of the designed vaccine. These significant computational analyses indicated that our proposed vaccine candidate might activate suitable immune responses against malaria. However, in vitro and in vivo studies are essential for further validation.

show abstract

“…Similarly, ANGPTL3 is an attractive target for in vivo gene editing. Furthermore, anti‐dyslipidemia vaccine therapies targeting ANGPTL3 will be a hot research topic 183 . Of course, the long‐term safety and cost‐effectiveness of these agents remain to be demonstrated in ongoing and future clinical trials 137 …”

Section: Drug Development Of Targets Based On Gwas Wgs and Wes Discov...mentioning

confidence: 99%

Drug development advances in human genetics‐based targets

Zhang,

Yu,

et al. 2024

MedComm

View full text Add to dashboard Cite

Drug development is a long and costly process, with a high degree of uncertainty from the identification of a drug target to its market launch. Targeted drugs supported by human genetic evidence are expected to enter phase II/III clinical trials or be approved for marketing more quickly, speeding up the drug development process. Currently, genetic data and technologies such as genome‐wide association studies (GWAS), whole‐exome sequencing (WES), and whole‐genome sequencing (WGS) have identified and validated many potential molecular targets associated with diseases. This review describes the structure, molecular biology, and drug development of human genetics‐based validated beneficial loss‐of‐function (LOF) mutation targets (target mutations that reduce disease incidence) over the past decade. The feasibility of eight beneficial LOF mutation targets (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, and INHBE) as targets for drug discovery is mainly emphasized, and their research prospects and challenges are discussed. In conclusion, we expect that this review will inspire more researchers to use human genetics and genomics to support the discovery of novel therapeutic drugs and the direction of clinical development, which will contribute to the development of new drug discovery and drug repurposing.

show abstract

Deimmunization of flagellin for repeated administration as a vaccine adjuvant

Cited by 26 publications

References 50 publications

Studies on the structure and stimulating effect on Caco-2 cells of flagellin and its truncated proteins of Escherichia coli Nissle 1917

Studies on the structure and stimulating effect on Caco-2 cells of flagellin and its truncated proteins of Escherichia coli Nissle 1917

A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach

Drug development advances in human genetics‐based targets

Contact Info

Product

Resources

About