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

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 polcalcinspecific 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.

Virus-like particle vaccinology, from bench to bedside

“…Conjugating the allergen to VLPs not only increased allergenspecific IgG responses but also strongly reduced the ability of the allergens to cause allergic reactions, an important safety feature of this new specific immunotherapy approach [85]. Similar findings were made with allergens displayed on HBcAg [86].…”

Chimeric Hepatitis B core virus-like particles harboring SARS-CoV2 epitope elicit a humoral immune response in mice

“…It is possible to insert the immunogenic epitopes in various regions of HBc, including the N-terminal, C-terminal, and MIR; however, the researchers mostly use the MIR region [ 26 – 28 ]. This region is known as the major insertion site with high efficiency in epitope presenting at the tips of VLP along with maintaining the self-assembling characteristic and is ideally able to trigger a vigorous immune response according to a particular antigen [ 29 , 30 ]. According to the preferable features of the MIR region, we constructed the chimeric protein based on the MIR insertion type for this investigation.…”

Heterologous expression of Chimeric hepatitis B core virus like particles harboring SARS-CoV2 epitope and evaluation of its immunization potential in mice

“…It is possible to insert the immunogenic epitopes in various regions of HBc, including the N-terminal, C-terminal, and MIR; however, the MIR region is the most widely applied by researchers [26, 27,28]. This region is known as the major insertion site with high e ciency in epitope presenting at the tips of VLP along with maintaining the self-assembling characteristic and is ideally able to trigger a vigorous immune response according to a particular antigen [29,30]. According to the preferable features of the MIR region, we constructed the chimeric protein based on the MIR insertion type for this investigation.…”