Immunoinformatic prediction of potential immunodominant epitopes from cagW in order to investigate protection against Helicobacter pylori infection based on experimental consequences

Abstract Helicobacter pylori is a leading cause of stomach cancer and peptic ulcers. Thus, identifying epitopes in H. pylori antigens is important for disease etiology, immunological surveillance, enhancing early detection tests, and developing optimal epitope-based vaccines. We used immunoinformatic and computational methods to create a potential CagW epitope candidate for H. pylori protection. The cagW gene of H. pylori was amplified and cloned into pcDNA3.1 (+) for injection into the muscles of healthy BALB/c mice to assess the impact of the DNA vaccine on interleukin levels. The results will be compared to a control group of mice that received PBS or cagW-pcDNA3.1 (+) vaccinations. An analysis of CagW protein antigens revealed 8 CTL and 7 HTL epitopes linked with AYY and GPGPG, which were enhanced by adding B-defensins to the N-terminus. The vaccine’s immunogenicity, allergenicity, and physiochemistry were validated, and its strong activation of TLRs (1, 2, 3, 4, and 10) suggests it is antigenic. An in-silico cloning and immune response model confirmed the vaccine’s expression efficiency and predicted its impact on the immune system. An immunofluorescence experiment showed stable and bioactive cagW gene expression in HDF cells after cloning the whole genome into pcDNA3.1 (+). In vivo vaccination showed that pcDNA3.1 (+)-cagW-immunized mice had stronger immune responses and a longer plasmid DNA release window than control-plasmid-immunized mice. After that, bioinformatics methods predicted, developed, and validated the three-dimensional structure. Many online services docked it with Toll-like receptors. The vaccine was refined using allergenicity, antigenicity, solubility, physicochemical properties, and molecular docking scores. Virtual-reality immune system simulations showed an impressive reaction. Codon optimization and in-silico cloning produced E. coli-expressed vaccines. This study suggests a CagW epitopes-protected H. pylori infection. These studies show that the proposed immunization may elicit particular immune responses against H. pylori, but laboratory confirmation is needed to verify its safety and immunogenicity..

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:23

Enthalten in:

Functional & integrative genomics - 23(2023), 2 vom: 29. März

Sprache:

Englisch

Beteiligte Personen:

Chehelgerdi, Matin [VerfasserIn]
Heidarnia, Fatemeh [VerfasserIn]
Dehkordi, Fereshteh Behdarvand [VerfasserIn]
Chehelgerdi, Mohammad [VerfasserIn]
Khayati, Shahoo [VerfasserIn]
Khorramian-Ghahfarokhi, Milad [VerfasserIn]
Kabiri-Samani, Saber [VerfasserIn]
Kabiri, Hamidreza [VerfasserIn]

Links:

Volltext [lizenzpflichtig]

BKL:

42.13$jMolekularbiologie

44.48$jMedizinische Genetik

Themen:

CTL
CagW protein
HTL
Helicobacter Pylori
MHC binding
Toll-like receptors

Anmerkungen:

© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

doi:

10.1007/s10142-023-01031-1

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2143911777

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