A bivalent dendrimeric peptide bearing a T-cell epitope from foot-and-mouth disease virus protein 3A improves humoral response against classical swine fever virus

An approach based on a dendrimer display of B- and T-cell epitopes relevant for antibody induction has been shown to be effective as a foot-and-mouth disease (FMD) vaccine. B2T dendrimers combining two copies of the major FMD virus (FMDV) type O B-cell epitope (capsid proteinVP1 (140–158)) covalently linked to a heterotypic T-cell epitope from non-structural protein 3A (21–35), henceforth B2T-3A, has previously been shown to elicit high neutralizing antibody (nAb) titers and IFN-γ-producing cells in both mice and pigs. Here, we provide evidence that the B- and T-cell epitopes need to be tethered to a single molecular platform for successful T-cell help, leading to efficient nAb induction in mice. In addition, mice immunized with a non-covalent mixture of B2T-3A dendrimers containing the B-cell epitopes of FMDV types O and C induced similarly high nAb levels against both serotypes, opening the way for a multivalent vaccine platform against a variety of serologically different FMDVs. These findings are relevant for the design of vaccine strategies based on B- and T-cell epitope combinations.

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Heat inactivation of foot-and-mouth disease virus, swine vesicular disease virus and classical swine fever virus when air-dried on plastic and glass surfaces

Biosafety and Health ◽

10.1016/j.bsheal.2021.07.002 ◽

2021 ◽

Author(s):

Thea Kristensen ◽

Graham J. Belsham ◽

Kirsten Tjørnehøj

Keyword(s):

Disease Virus ◽

Classical Swine Fever Virus ◽

Foot And Mouth Disease ◽

Classical Swine Fever ◽

Mouth Disease ◽

Heat Inactivation ◽

Swine Vesicular Disease Virus ◽

Mouth Disease Virus ◽

Glass Surfaces ◽

Vesicular Disease

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Designing Functionally Versatile, Highly Immunogenic Peptide-Based Multiepitopic Vaccines against Foot-and-Mouth Disease Virus

Vaccines ◽

10.3390/vaccines8030406 ◽

2020 ◽

Vol 8 (3) ◽

pp. 406

Author(s):

Sira Defaus ◽

Mar Forner ◽

Rodrigo Cañas-Arranz ◽

Patricia de León ◽

María J. Bustos ◽

...

Keyword(s):

T Cell ◽

Disease Virus ◽

Animal Health ◽

Unmet Need ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitopes ◽

Mouth Disease Virus ◽

Foot And Mouth

A broadly protective and biosafe vaccine against foot-and-mouth disease virus (FMDV) remains an unmet need in the animal health sector. We have previously reported solid protection against serotype O FMDV afforded by dendrimeric peptide structures harboring virus-specific B- and T-cell epitopes, and also shown such type of multivalent presentations to be advantageous over simple B-T-epitope linear juxtaposition. Chemically, our vaccine platforms are modular constructions readily made from specified B- and T-cell epitope precursor peptides that are conjugated in solution. With the aim of developing an improved version of our formulations to be used for on-demand vaccine applications, we evaluate in this study a novel design for epitope presentation to the immune system based on a multiple antigen peptide (MAP) containing six immunologically relevant motifs arranged in dendrimeric fashion (named B2T-TB2). Interestingly, two B2T units fused tail-to-tail into a single homodimer platform elicited higher B- and T-cell specific responses than former candidates, with immunization scores remaining stable even after 4 months. Moreover, this macromolecular assembly shows consistent immune response in swine, the natural FMDV host, at reduced dose. Thus, our versatile, immunogenic prototype can find application in the development of peptide-based vaccine candidates for various therapeutic uses using safer and more efficacious vaccination regimens.

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Common Host Factors Involved in the Function of the Foot-and-mouth Disease Virus and Classical Swine Fever Virus Internal Ribosomal Entry Sites

10.21203/rs.3.rs-327980/v1 ◽

2021 ◽

Author(s):

Yutaro Ide ◽

Nobumasa Ito ◽

Takafumi Matsui ◽

Kyoko Tsukiyama-Kohara

Keyword(s):

Disease Virus ◽

Classical Swine Fever Virus ◽

Foot And Mouth Disease ◽

Classical Swine Fever ◽

Host Factor ◽

Mouth Disease ◽

Fever Virus ◽

Host Factors ◽

Mouth Disease Virus ◽

Ires Element

Abstract Foot-and-mouth disease virus (FMDV) and classical swine fever virus (CSFV) both possess positive strand RNA genomes and an internal ribosomal entry site (IRES) element within their 5¢-untranslated regions. To identify common host factors involved with the activity of these IRESes, we utilized cell lines expressing a bicistronic luciferase reporter plasmid, which contained an FMDV-IRES or CSFV-IRES element between the Renilla and firefly luciferase genes. First, we treated FMDV-IRES cells with French maritime pine extract, Pycnogenol® (PYC), and evaluated its suppressive effect on FMDV-IRES activity, as anti-viral effect of PYC was reported so far. We next performed microarray analysis to identify host factors affected by PYC, and confirmed host-factor-IRES interaction by applying host factor-specific siRNAs. We found that polycystic kidney disease 1-like 3 (PKD1L3) and ubiquitin specific peptidase 31 (USP31) are involved in FMDV-IRES activity. Moreover, silencing of these factors also significantly suppressed CSFV-IRES activity. Accordingly, we suggest that PKD1L3 and USP31 are host factors that are involved in the function of the FMDV and CSFV-IRES elements.

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A Single Dose of Dendrimer B2T Peptide Vaccine Partially Protects Pigs against Foot-and-Mouth Disease Virus Infection

Vaccines ◽

10.3390/vaccines8010019 ◽

2020 ◽

Vol 8 (1) ◽

pp. 19 ◽

Cited By ~ 6

Author(s):

Rodrigo Cañas-Arranz ◽

Mar Forner ◽

Sira Defaus ◽

Patricia de León ◽

María J. Bustos ◽

...

Keyword(s):

Single Dose ◽

T Cell ◽

Disease Virus ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Single Shot ◽

Post Immunization ◽

Mouth Disease Virus ◽

Foot And Mouth

Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals whose control relies on efficient vaccination. We have reported that dendrimer peptide B2T, with two copies of FMDV B-cell epitope VP1 (136–154) linked through maleimide units to T-cell epitope 3A (21–35)], elicits potent B- and T-cell specific responses and confers solid protection in pigs to type-O FMDV challenge after two doses of peptide. Herein we now show that B2T evokes specific protective immune responses after administration of a single dose of either 2 or 0.5 mg of peptide. High titers of ELISA and neutralizing antibodies against FMDV were detectable at day 15 post-immunization. Likewise, activated T cells and induced IFN-γ response to in vitro recall with FMDV peptides were also detected by the same day. Further, in 70% of B2T-vaccinated pigs, full protection—no clinical signs of disease—was observed upon virus challenge at day 25 post-immunization. These results strengthen the potential of B2T as a safe, cost-effective candidate vaccine conferring adequate protection against FMDV with a single dose. The finding is particularly relevant to emergency scenarios permitting only a single shot immunization.

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