Synthesis and Immunological Evaluation of Virus-Like Particle-Milbemycin A3/A4 Conjugates

Zeltiņš, Andris; Turks, Māris; Skrastiņa, Dace; Lugiņina, Jevgeņija; Kalnciema, Ieva; Baļķe, Ina; Bizdēna, Ērika; Skrivelis, V

doi:10.3390/antibiotics6030018

Cited by 4 publications

(2 citation statements)

References 22 publications

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“…As illustrate by the accumulation of the CD203c marker. Our results are in line with previous reports and particularly with an earlier publication on VLP presenting the major cat allergen Fel d 1 on its surface [ 73 , 84 , 85 ].…”

Section: Discussionsupporting

confidence: 94%

Design, production and immunomodulatory potency of a novel allergen bioparticle

Gomord¹,

Stordeur²,

Fitchette³

et al. 2020

PLoS ONE

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Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. To become a more attractive alternative to lifelong symptomatic drug use, improvements to AIT are needed. Among the most promising new immunotherapy strategies is the use of bioparticles for the presentation of target antigen to the immune system as they can elicit strong T cell and B cell immune responses. Virus-like particles (VLPs) are a specific class of bioparticles in which the structural and immunogenic constituents are from viral origin. However, VLPs are ill-suited for use in AIT as their antigenicity is linked to structure. Recently, synthetic biology has been used to produce artificial modular bioparticles, in which supramolecular assemblies are made of elements from heterogeneous biological sources promoting the design and use of in vivo-assembling enveloped bioparticles for viral and non-viral antigens presentation. We have used a coiled-coil hybrid assembly for the design of an enveloped bioparticle (eBP) that present trimers of the Der p 2 allergen at its surface, This bioparticle was produced as recombinant and in vivo assembled eBPs in plant. This allergen biotherapeutic was used to demonstrate i) the capacity of plants to produce synthetic supramolecular allergen bioparticles, and ii) the immunomodulatory potential of naturally-assembled allergen bioparticles. Our results show that allergens exposed on eBPs induced a very strong IgG response consisting predominantly of IgG2a in favor of the TH1 response. Finally, our results demonstrate that rDer p 2 present on the surface of BPs show a very limited potential to stimulate the basophil degranulation of patient allergic to this allergen which is predictive of a high safety potential.

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Section: Discussionsupporting

confidence: 94%

Design, production and immunomodulatory potency of a novel allergen bioparticle

Gomord¹,

Stordeur²,

Fitchette³

et al. 2020

PLoS ONE

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“…Our previous results using filamentous VLPs, derived from potato virus Y (PVY) as a vaccine carrier for the hepatitis B viral (HBV) preS1 epitope, demonstrated a strong anti-preS1 immune response, even in the absence of adjuvants [18]. Furthermore, PVY VLPs contain several surface exposed lysins that have been used for the successful chemical coupling of milbemycin A3/A4 derivatives [19]. These data suggest the potential use of PVY VLPs as a new antigen-displaying platform.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Bacterial Expression Systems Based on Potato Virus Y-like Particles for Vaccine Generation

et al. 2022

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Plant-based virus-like particle (VLP) vaccines have been studied for years, demonstrating their potential as antigen-presenting platforms. In this paper, we describe the development of, and compare between, simple Escherichia coli-based antigen display platforms for the generation of potato virus Y (PVY) VLP-derived vaccines, thus allowing the production of vaccines from a single bacterial cell culture. We constructed four systems with the major cat allergen Fel d 1; namely, direct fusion with plant virus PVY coat protein (CP), mosaic PVY VLPs, and two coexpression variants of conjugates (SpyTag/SpyCatcher) allowing coexpression and conjugation directly in E. coli cells. For control experiments, we included PVY VLPs chemically coupled with Fel d 1. All constructed PVY–Fel d 1 variants were well expressed and soluble, formed PVY-like filamentous particles, and were recognized by monoclonal Fel d 1 antibodies. Our results indicate that all vaccine variants induced high titers of anti-Fel d 1 antibodies in murine models. Mice that were immunized with the chemically coupled Fel d 1 antigen exhibited the highest antibody titers and antibody–antigen interaction specificity, as detected by binding avidity and recognition of native Fel d 1. IgG1 subclass antibodies were found to be the dominant IgG class against PVY–Fel d 1. PVY CP-derived VLPs represent an efficient platform for the comparison of various antigen presentation systems to help evaluate different vaccine designs.

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Tannic Acid, as a Structural Moiety Coupled to a Protein Antigen, Exhibiting a Molecular-structure Adjuvant Activity for Antibody Specificity Enhancement

Pedroza-Escobar

Molina-Ramírez

Cabral-Hipólito

et al. 2022

PPL

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Background: An antigen is a small foreign substance, such a microorganism structural-protein, that may trigger an immune response once inside the body. Antigens are preferentially used rather than a complete attenuated microorganism to develop safe vaccines. Unfortunately, not all antigens are able of inducing an immune response. Thus, new adjuvants seeking to enhance the antigen’s ability to stimulate immunity must be developed. Therefore,the objective of this work was to evaluate the molecular-structure adjuvant activity of tannic acid (TA) coupled to a protein antigen in Balb/c mice. Method: Bovine serum albumin (BSA) was used as an antigen. The coupling of BSA and TA was mediated by carbodiimide crosslinking, and verified by SDS-PAGE. Forty-two Balb/c mice were divided into seven groups including two controls without antigen, an antigen control, an adjuvant control, and two treatment groups. An additional group was used for macrophages isolation. A 30-day scheme was used to immunize the mice. The analysis of humoral immunity included immunoglobulin quantification, isotyping and antigen-antibody precipitation. The analysis of cell-mediated immunity included the quantification of nitric oxide from peritoneal macrophages and splenocytes’ proliferation assay, after treatment stimulation. Results: No differences were found in the antibodies’ concentration or isotypes induced with the conjugate or the pure BSA. However, an immunogenicity improvement (p<0.05) was observed through the specific anti-BSA antibody titles in mice immunized with the conjugate. Besides, macrophage activation (p<0.05) was detected when stimulated with the treatments containing TA. Conclusion: Tannic acid exhibited macrophages’ activation properties. Moreover, when TA is incorporated into the structure of a protein antigen such as BSA, an antibody specificity enhancement is observed. This as a consequence of antigen processing by activated antigen-presenting cells. These results showed the use of tannic acid as a novel candidate for vaccine molecular-structure adjuvant.

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Synthesis and Immunological Evaluation of Virus-Like Particle-Milbemycin A3/A4 Conjugates

Cited by 4 publications

References 22 publications

Design, production and immunomodulatory potency of a novel allergen bioparticle

Design, production and immunomodulatory potency of a novel allergen bioparticle

Comparison of Bacterial Expression Systems Based on Potato Virus Y-like Particles for Vaccine Generation

Tannic Acid, as a Structural Moiety Coupled to a Protein Antigen, Exhibiting a Molecular-structure Adjuvant Activity for Antibody Specificity Enhancement

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