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Genetically engineered fusion of allergen and viral-like particle induces a more effective allergen-specific immune response than a combination of them

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Abstract

Chimeric virus-like particles (VLPs) were developed as a candidate for allergen-specific immunotherapy. In this study, hepatitis B core antigen (HBcAg) that genetically fused to Chenopodium album polcalcin (Che a 3)–derived peptide was expressed in E. coli BL21, purified, and VLP formation was evaluated using native agarose gel electrophoresis (NAGE) and transmission electron microscopy (TEM). Chimeric HBc VLPs were characterized in terms of their reactivity to IgE, the induction of blocking IgG and allergen-specific IgE, basophil-activating capacity, and Th1-type immune responses. Results from IgE reactivity and basophil activation test showed that chimeric HBc VLPs lack IgE-binding capacity and basophil degranulation activity. Although chimeric HBc VLPs induced the highest level of efficient polcalcin-specific IgG antibody in comparison to those induced by recombinant Che a 3 (rChe a 3) mixed either with HBc VLPs or alum, they triggered the lowest level of polcalcin-specific IgE in mice following immunization. Furthermore, in comparison to the other antigens, chimeric HBc VLPs produced a polcalcin-specific Th1 cell response. Taken together, genetically fusion of allergen derivatives to HBc VLPs, in comparison to a mix of them, may be a more effective way to induce appropriate immune responses in allergen-specific immunotherapy.

Key points

• The insertion of allergen-derived peptide into major insertion region (MIR) of hepatitis B virus core (HBc) antigen resulted in nanoparticles displaying allergen-derived peptide upon its expression in prokaryotic host.

• The resultant VLPs (chimeric HBc VLPs) did not exhibit IgE reactivity with allergic patients’ sera and were not able to degranulate basophils.

• Chimeric HBc VLPs dramatically improved protective IgG antibody response compared with those induced by allergen mixed either with HBc VLPs or alum.

• Chimeric HBc VLPs induced Th1 responses that were counterparts of Th2 responses (allergic).

• Chimeric HBc VLPs increased IgG2a/ IgG1 ratio and the level of IFN-γ compared to those induced by allergen mixed with either HBc VLPs or alum.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the manuscript.

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Funding

The Bushehr University of Medical Sciences provided this work a research budget. This study is the MS thesis of the first author and was supported by a research grant (code: 1218) from Bushehr University of Medical Sciences.

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MM, IN, and SJM conceived and designed research. MZ, AB, NM, PD, JA, SH, Kh H, and FO conducted experiments. MM, SJM, and SA contributed new reagents or analytical tools. AM and GR analyzed data. MM and SJM wrote the manuscript. All authors read and approved the manuscript.

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Correspondence to Mohsen Mohammadi.

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In case animals: All animal dealings in this study were performed under protocol approved by the Animal Care and Use Committee of Bushehr University of Medical Sciences–Iran (Permit number: IR.BPUMS.REC.1397.011). The animal procedures were in accordance with the Specific National Ethical Guidelines for Biomedical Research issued by the Research and Technology Deputy of Ministry of Health and Medicinal Education (MOHME) of Iran (issued in 2005).

In case human: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee, Bushehr University of Medical Sciences with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Sani, M.Z., Bargahi, A., Momenzadeh, N. et al. Genetically engineered fusion of allergen and viral-like particle induces a more effective allergen-specific immune response than a combination of them. Appl Microbiol Biotechnol 105, 77–91 (2021). https://doi.org/10.1007/s00253-020-11012-0

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