Chimeric RHDV Virus-Like Particles Displaying Foot-and-Mouth Disease Virus Epitopes Elicit Neutralizing Antibodies and Confer Partial Protection in Pigs

Currently there is a clear trend towards the establishment of virus-like particles (VLPs) as a powerful tool for vaccine development. VLPs are tunable nanoparticles that can be engineered to be used as platforms for multimeric display of foreign antigens. We have previously reported that VLPs derived from rabbit hemorrhagic disease virus (RHDV) constitute an excellent vaccine vector, capable of inducing specific protective immune responses against inserted heterologous T-cytotoxic and B-cell epitopes. Here, we evaluate the ability of chimeric RHDV VLPs to elicit immune response and protection against Foot-and-Mouth disease virus (FMDV), one of the most devastating livestock diseases. For this purpose, we generated a set of chimeric VLPs containing two FMDV-derived epitopes: a neutralizing B-cell epitope (VP1 (140–158)) and a T-cell epitope [3A (21–35)]. The epitopes were inserted joined or individually at two different locations within the RHDV capsid protein. The immunogenicity and protection potential of the chimeric VLPs were analyzed in the mouse and pig models. Herein we show that the RHDV engineered VLPs displaying FMDV-derived epitopes elicit a robust neutralizing immune response in mice and pigs, affording partial clinical protection against an FMDV challenge in pigs.

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Xenoepitope Substitution Avoids Deceptive Imprinting and Broadens the Immune Response to Foot-and-Mouth Disease Virus

Clinical and Vaccine Immunology ◽

10.1128/cvi.00035-12 ◽

2012 ◽

Vol 19 (4) ◽

pp. 461-467 ◽

Cited By ~ 5

Author(s):

Steven M. Szczepanek ◽

Roger W. Barrette ◽

Debra Rood ◽

Diana Alejo ◽

Lawrence K. Silbart

Keyword(s):

Immune Response ◽

B Cell ◽

Disease Virus ◽

Rational Design ◽

Rna Viruses ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

Decoy Epitope

ABSTRACTMany RNA viruses encode error-prone polymerases which introduce mutations into B and T cell epitopes, providing a mechanism for immunological escape. When regions of hypervariability are found within immunodominant epitopes with no known function, they are referred to as “decoy epitopes,” which often deceptively imprint the host's immune response. In this work, a decoy epitope was identified in the foot-and-mouth disease virus (FMDV) serotype O VP1 G-H loop after multiple sequence alignment of 118 isolates. A series of chimeric cyclic peptides resembling the type O G-H loop were prepared, each bearing a defined “B cell xenoepitope” from another virus in place of the native decoy epitope. These sequences were derived from porcine respiratory and reproductive syndrome virus (PRRSV), from HIV, or from a presumptively tolerogenic sequence from murine albumin and were subsequently used as immunogens in BALB/c mice. Cross-reactive antibody responses against all peptides were compared to a wild-type peptide and ovalbumin (OVA). A broadened antibody response was generated in animals inoculated with the PRRSV chimeric peptide, in which virus binding of serum antibodies was also observed. A B cell epitope mapping experiment did not reveal recognition of any contiguous linear epitopes, raising the possibility that the refocused response was directed to a conformational epitope. Taken together, these results indicate that xenoepitope substitution is a novel method for immune refocusing against decoy epitopes of RNA viruses such as FMDV as part of the rational design of next-generation vaccines.

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Peer Review #2 of "Immunogenicity evaluation of MS2 phage-mediated chimeric nanoparticle displaying an immunodominant B cell epitope of foot-and-mouth disease virus (v0.1)"

10.7287/peerj.4823v0.1/reviews/2 ◽

2018 ◽

Keyword(s):

B Cell ◽

Peer Review ◽

Disease Virus ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

B Cell Epitope ◽

Mouth Disease Virus ◽

Foot And Mouth

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Peer Review #1 of "Immunogenicity evaluation of MS2 phage-mediated chimeric nanoparticle displaying an immunodominant B cell epitope of foot-and-mouth disease virus (v0.1)"

10.7287/peerj.4823v0.1/reviews/1 ◽

2018 ◽

Author(s):

D Rowlands

Keyword(s):

B Cell ◽

Peer Review ◽

Disease Virus ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

B Cell Epitope ◽

Mouth Disease Virus ◽

Foot And Mouth

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Inclusion of a specific T cell epitope increases the protection conferred against foot-and-mouth disease virus in pigs by a linear peptide containing an immunodominant B cell site

Virology Journal ◽

10.1186/1743-422x-9-66 ◽

2012 ◽

Vol 9 (1) ◽

pp. 66 ◽

Cited By ~ 13

Author(s):

Carolina Cubillos ◽

Beatriz G de la Torre ◽

Juan Bárcena ◽

David Andreu ◽

Francisco Sobrino ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Disease Virus ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

T Cell Epitope ◽

Linear Peptide ◽

Mouth Disease Virus ◽

Foot And Mouth

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Salmonella Vaccine Vector System for Foot-and-Mouth Disease Virus and Evaluation of Its Efficacy with Virus-Like Particles

Vaccines ◽

10.3390/vaccines9010022 ◽

2021 ◽

Vol 9 (1) ◽

pp. 22

Author(s):

Yong Zhi ◽

Hyun Jung Ji ◽

Huichen Guo ◽

Jae Hyang Lim ◽

Eui-Baek Byun ◽

...

Keyword(s):

Disease Virus ◽

Cell Epitope ◽

Foot And Mouth Disease ◽

Mouth Disease ◽

Vector System ◽

Th2 Cells ◽

Virus Like Particles ◽

Mouth Disease Virus ◽

Foot And Mouth ◽

Ifn Γ

Foot-and-mouth disease virus (FMDV) causes a highly contagious and devastating disease in livestock animals and has a great potential to cause severe economic loss worldwide. The major antigen of FMDV capsid protein, VP1, contains the major B-cell epitope responsible for effectively eliciting protective humoral immunity. In this study, irradiated Salmonella Typhimurium (KST0666) were used as transgenic vectors containing stress-inducible plasmid pRECN-VP1 to deliver the VP1 protein from FMDV-type A/WH/CHA/09. Mice were orally inoculated with ATOMASal-L3 harboring pRECN-VP1, and FMDV virus-like particles, where (VLPFMDV)-specific humoral, mucosal, and cellular immune responses were evaluated. Mice vaccinated with attenuated Salmonella (KST0666) expressing VP1 (named KST0669) showed high levels of VLP-specific IgA in feces and IgG in serum, with high FMDV neutralization titer. Moreover, KST0669-vaccinated mice showed increased population of IFN-γ (type 1 T helper cells; Th1 cells)-, IL-5 (Th2 cells)-, and IL-17A (Th17 cells)-expressing CD4+ as well as activated CD8+ T cells (IFN-γ+CD8+ cells), detected by stimulating VLPFMDV. All data indicate that our Salmonella vector system successfully delivered FMDV VP1 to immune cells and that the humoral and cellular efficacy of the vaccine can be easily evaluated using VLPFMDV in a Biosafety Level I (BSL1) laboratory.

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