Immunogenicity of adenovirus-derived porcine parvovirus-like particles displaying B and T cell epitopes of foot-and-mouth disease

Synthetic peptides incorporating protective B- and T-cell epitopes are candidates for new safer foot-and-mouth disease (FMD) vaccines. We have reported that dendrimeric peptides including four copies of a B-cell epitope (VP1 136 to 154) linked to a T-cell epitope (3A 21 to 35) of FMD virus (FMDV) elicit potent B- and T-cell specific responses and confer protection to viral challenge, while juxtaposition of these epitopes in a linear peptide induces less efficient responses. To assess the relevance of B-cell epitope multivalency, dendrimers bearing two (B2T) or four (B4T) copies of the B-cell epitope from type O FMDV (a widespread circulating serotype) were tested in CD1 mice and showed that multivalency is advantageous over simple B-T-epitope juxtaposition, resulting in efficient induction of neutralizing antibodies and optimal release of IFNγ. Interestingly, the bivalent B2T construction elicited similar or even better B- and T-cell specific responses than tetravalent B4T. In addition, the presence of the T-cell epitope and its orientation were shown to be critical for the immunogenicity of the linear juxtaposed monovalent peptides analyzed in parallel. Taken together, our results provide useful insights for a more accurate design of FMD subunit vaccines.

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A peptide construct containing B-cell and T-cell epitopes from the foot-and-mouth disease viral VP1 protein induces efficient antiviral protection

Vaccine ◽

10.1016/s0264-410x(98)00236-9 ◽

1999 ◽

Vol 17 (6) ◽

pp. 577-584 ◽

Cited By ~ 17

Author(s):

O.M Volpina ◽

A.Yu Surovoy ◽

M.N Zhmak ◽

M.A Kuprianova ◽

D.O Koroev ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitopes ◽

Vp1 Protein ◽

Foot And Mouth

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Identification of T-Cell Epitopes in Nonstructural Proteins of Foot-and-Mouth Disease Virus

Journal of Virology ◽

10.1128/jvi.75.7.3164-3174.2001 ◽

2001 ◽

Vol 75 (7) ◽

pp. 3164-3174 ◽

Cited By ~ 60

Author(s):

E. Blanco ◽

M. Garcia-Briones ◽

A. Sanz-Parra ◽

P. Gomes ◽

E. De Oliveira ◽

...

Keyword(s):

T Cell ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitopes ◽

Nonstructural Proteins ◽

Mouth Disease Virus ◽

Foot And Mouth

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A 10-Amino-Acid Linear Sequence of VP1 of Foot and Mouth Disease Virus Containing B- and T-Cell Epitopes Induces Protection in Mice

Virology ◽

10.1006/viro.1995.1519 ◽

1995 ◽

Vol 212 (2) ◽

pp. 614-621 ◽

Cited By ~ 40

Author(s):

P. Zamorano ◽

A. Wigdorovitz ◽

M. Perez-Filgueira ◽

C. Carrillo ◽

J.M. Escribano ◽

...

Keyword(s):

Amino Acid ◽

T Cell ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitopes ◽

Linear Sequence ◽

Mouth Disease Virus ◽

Foot And Mouth

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Identification of novel foot-and-mouth disease virus specific T-cell epitopes in c/c and d/d haplotype miniature swine

Virus Research ◽

10.1016/j.virusres.2006.05.006 ◽

2006 ◽

Vol 121 (2) ◽

pp. 223-228 ◽

Cited By ~ 40

Author(s):

Wilhelm Gerner ◽

Michael S. Denyer ◽

Haru-Hisa Takamatsu ◽

Thomas E. Wileman ◽

Karl-Heinz Wiesmüller ◽

...

Keyword(s):

T Cell ◽

Disease Virus ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitopes ◽

Miniature Swine ◽

Mouth Disease Virus ◽

Foot And Mouth

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Immunogenicity of Foot-and-Mouth Disease Virus Dendrimer Peptides: Need for a T-Cell Epitope and Ability to Elicit Heterotypic Responses

Molecules ◽

10.3390/molecules26164714 ◽

2021 ◽

Vol 26 (16) ◽

pp. 4714

Author(s):

Rodrigo Cañas-Arranz ◽

Patricia de León ◽

Sira Defaus ◽

Elisa Torres ◽

Mar Forner ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitope ◽

T Cell Epitopes ◽

Vaccine Platform ◽

Mouth Disease Virus ◽

Foot And Mouth

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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Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health

Vaccines ◽

10.3390/vaccines9050477 ◽

2021 ◽

Vol 9 (5) ◽

pp. 477

Author(s):

Mar Forner ◽

Rodrigo Cañas-Arranz ◽

Sira Defaus ◽

Patricia de León ◽

Miguel Rodríguez-Pulido ◽

...

Keyword(s):

T Cell ◽

Animal Health ◽

Foot And Mouth Disease ◽

Infectious Agent ◽

Mouth Disease ◽

Cold Chain ◽

Attractive Alternative ◽

T Cell Epitopes ◽

Mouth Disease Virus ◽

Foot And Mouth

Vaccines are considered one of the greatest global health achievements, improving the welfare of society by saving lives and substantially reducing the burden of infectious diseases. However, few vaccines are fully effective, for reasons ranging from intrinsic limitations to more contingent shortcomings related, e.g., to cold chain transport, handling and storage. In this context, subunit vaccines where the essential antigenic traits (but not the entire pathogen) are presented in rationally designed fashion have emerged as an attractive alternative to conventional ones. In particular, this includes the option of fully synthetic peptide vaccines able to mimic well-defined B- and T-cell epitopes from the infectious agent and to induce protection against it. Although, in general, linear peptides have been associated to low immunogenicity and partial protection, there are several strategies to address such issues. In this review, we report the progress towards the development of peptide-based vaccines against foot-and-mouth disease (FMD) a highly transmissible, economically devastating animal disease. Starting from preliminary experiments using single linear B-cell epitopes, recent research has led to more complex and successful second-generation vaccines featuring peptide dendrimers containing multiple copies of B- and T-cell epitopes against FMD virus or classical swine fever virus (CSFV). The usefulness of this strategy to prevent other animal and human diseases is discussed.

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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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