An Evaluation of Urease A Subunit Nanocapsules as a Vaccine in a Mouse Model of Helicobacter pylori Infection.
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ABSTRACT:
SUBMITTER: Skakic I
PROVIDER: S-EPMC10674275 | biostudies-literature | 2023 Oct
REPOSITORIES: biostudies-literature
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An Evaluation of Urease A Subunit Nanocapsules as a Vaccine in a Mouse Model of <i>Helicobacter pylori</i> Infection.
Skakic Ivana I Francis Jasmine E JE Dekiwadia Chaitali C Aibinu Ibukun I Huq Mohsina M Taki Aya C AC Walduck Anna A Smooker Peter M PM
Vaccines 20231027 11
Using removable silica templates, protein nanocapsules comprising the A subunit of <i>Helicobacter pylori</i> urease (UreA) were synthesised. The templates were of two sizes, with solid core mesoporous shell (SC/MS) silica templates giving rise to nanocapsules of average diameter 510 nm and mesoporous (MS) silica templates giving rise to nanocapsules of average diameter 47 nm. Both were shown to be highly monodispersed and relatively homogenous in structure. Various combinations of the nanocapsu ...[more]
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Project description:BackgroundHelicobacter Pylori (H. Pylori) is a pathogen that may invade the human stomach. This bacterial strain is now causing widespread concern and considerable health issues worldwide. In contrast to antibiotic treatment, which may lead to drug resistance, vaccination therapy is emerging as a possible immunotherapy option for H. Pylori. DNA vaccines are a potential option to traditional vaccines among vaccine research methods. Furthermore, the multiepitope DNA vaccination may induce a broader immune response to suppress H. Pylori infection.MethodsFour target antigenic proteins (outer membrane beta-barrel, outer membrane beta, HofA, and hcp beta-lactamase-like protein) were used to identify epitopes. The best B and T cell epitopes were selected to induce humoral and cellular immune responses and were connected using the HEYGAEALERAG and GGGS linkers. The peptide's physicochemical characteristics, secondary and tertiary structures, antigenicity, and allergenicity were evaluated utilizing several bioinformatics tools. The multiepitope peptide was successfully inserted into the pcDNA3.1 expression vector. The immunological responses of both the vaccinated and control groups were evaluated by measuring cytokines and antibodies.ResultsBased on the data, the multiepitope peptide consists of 278 amino acid residues and has an average molecular weight (MW) of 28643.61 Da. The peptide residues were mainly situated within the preferred and permitted areas of the Ramachandran plot, accounting for 92.86 % of the total. The VaxiJen server has calculated that the multiepitope peptide has an antigenicity score of 1.0067. BALB/c mice vaccinated with the DNA vaccine produced significantly higher levels of specific IgG antibodies (p < 0.05). The vaccinated mice exhibited a TH1-type cellular immune response characterized by the generation of IFN-γ and a longer length of life compared to the control animals (p < 0.05). In addition, the vaccination group exhibited a substantial increase in the expression level of IFN-γ and IL-1β genes compared to the control group (p < 0.05).ConclusionsThe results demonstrated that the multiepitope DNA vaccine elicited significant humoral and cellular responses, and increased survival time in BALB/c mice, indicating that selecting potential epitopes may be a viable technique for developing multiepitope-based vaccines. This can help to introduce effective vaccines.
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Project description:More than 80% of gastric cancer is attributable to stomach infection with Helicobacter pylori (Hp). Gastric preneoplastic progression involves sequential tissue changes, including loss of parietal cells, metaplasia and dysplasia. In transgenic mice, active KRAS expression recapitulates these tissue changes in the absence of Hp infection. This model provides an experimental system to investigate additional roles of Hp in preneoplastic progression, beyond its known role in initiating inflammation. Tissue histology, gene expression, the immune cell repertoire, and metaplasia and dysplasia marker expression were assessed in KRAS+ mice +/-Hp infection. Hp+/KRAS+ mice had severe T-cell infiltration and altered macrophage polarization; a different trajectory of metaplasia; more dysplastic glands; and greater proliferation of metaplastic and dysplastic glands. Eradication of Hp with antibiotics, even after onset of metaplasia, prevented or reversed these tissue phenotypes. These results suggest that gastric preneoplastic progression differs between Hp+ and Hp- cases, and that sustained Hp infection can promote the later stages of gastric preneoplastic progression.
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