DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses
Despite foot-and-mouth disease virus (FMDV) being responsible for one of the most devastating animal diseases, little is known about the cellular immune mechanisms involved in protection against this virus. In this work we have studied the potential of DNA vaccines based on viral minigenes corresponding to three major B and T-cell FMDV epitopes (isolate C-S8c1) originally identified in natural hosts. The BTT epitopes [VP1 (133-156)-3A (11-40)-VP4 (20-34)] were cloned into the plasmid pCMV, either alone or fused to ubiquitin, the lysosomal targeting signal from LIMPII, a soluble version of CTLA4 or a signal peptide from the human prion protein, to analyze the effect of processing through different antigenic presentation pathways on the immunogenicity of the FMDV epitopes. As a first step in the analysis of modulation exerted by these target signals, a FMDV infection inhibition assay in Swiss outbred mice was developed and used to analyze the protection conferred by the different BTT-expressing plasmids. Only one of the 37 mice immunized with minigene-bearing plasmids developed specific neutralizing antibodies prior to FMDV challenge. As expected, this single mouse that had been immunized with the BTT tandem epitopes fused to a signal peptide (pCMV-spBTT) was protected against FMDV infection. Interestingly, nine more of the animals immunized with BTT-expressing plasmids did not show viremia at 48 h post-infection (pi), even in the absence of anti-FMDV antibodies prior to challenge. The highest protection (50%, six out of 12 mice) was observed with the plasmid expressing BTT alone, indicating that the targeting strategies used did not result in an improvement of the protection conferred by BTT epitopes. Interestingly, peptide specific CD4+ T-cells were detected for some of the BTT-protected mice. Thus, a DNA vaccine based on single FMDV B and T cell epitopes can protect mice, in the absence of specific antibodies at the time of challenge. Further work must be done to elucidate the mechanisms involved in protection and to determine the protective potential of these vaccines in natural FMDV hosts. © 2006 Elsevier Ltd. All rights reserved.
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2006
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Subjects: | Vaccine, Protection, DNA immunization, Foot-and-mouth disease virus, Cellular immune response, Serum neutralization, Mouse model, |
Online Access: | http://hdl.handle.net/20.500.12792/4910 http://hdl.handle.net/10261/294811 |
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dig-inia-es-10261-2948112023-02-20T10:42:14Z DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses Borrego, B. Fernandez-Pacheco, P. Ganges, L. Domenech, N. Fernandez-Borges, N. Sobrino, F. Rodríguez, F. Vaccine Protection DNA immunization Foot-and-mouth disease virus Cellular immune response Serum neutralization Mouse model Despite foot-and-mouth disease virus (FMDV) being responsible for one of the most devastating animal diseases, little is known about the cellular immune mechanisms involved in protection against this virus. In this work we have studied the potential of DNA vaccines based on viral minigenes corresponding to three major B and T-cell FMDV epitopes (isolate C-S8c1) originally identified in natural hosts. The BTT epitopes [VP1 (133-156)-3A (11-40)-VP4 (20-34)] were cloned into the plasmid pCMV, either alone or fused to ubiquitin, the lysosomal targeting signal from LIMPII, a soluble version of CTLA4 or a signal peptide from the human prion protein, to analyze the effect of processing through different antigenic presentation pathways on the immunogenicity of the FMDV epitopes. As a first step in the analysis of modulation exerted by these target signals, a FMDV infection inhibition assay in Swiss outbred mice was developed and used to analyze the protection conferred by the different BTT-expressing plasmids. Only one of the 37 mice immunized with minigene-bearing plasmids developed specific neutralizing antibodies prior to FMDV challenge. As expected, this single mouse that had been immunized with the BTT tandem epitopes fused to a signal peptide (pCMV-spBTT) was protected against FMDV infection. Interestingly, nine more of the animals immunized with BTT-expressing plasmids did not show viremia at 48 h post-infection (pi), even in the absence of anti-FMDV antibodies prior to challenge. The highest protection (50%, six out of 12 mice) was observed with the plasmid expressing BTT alone, indicating that the targeting strategies used did not result in an improvement of the protection conferred by BTT epitopes. Interestingly, peptide specific CD4+ T-cells were detected for some of the BTT-protected mice. Thus, a DNA vaccine based on single FMDV B and T cell epitopes can protect mice, in the absence of specific antibodies at the time of challenge. Further work must be done to elucidate the mechanisms involved in protection and to determine the protective potential of these vaccines in natural FMDV hosts. © 2006 Elsevier Ltd. All rights reserved. 2023-02-20T10:42:14Z 2023-02-20T10:42:14Z 2006 journal article Vaccine 24(18): 3889-3899 (2006) 0264-410X http://hdl.handle.net/20.500.12792/4910 http://hdl.handle.net/10261/294811 10.1016/j.vaccine.2006.02.028 en none Elsevier |
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Vaccine Protection DNA immunization Foot-and-mouth disease virus Cellular immune response Serum neutralization Mouse model Vaccine Protection DNA immunization Foot-and-mouth disease virus Cellular immune response Serum neutralization Mouse model |
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Vaccine Protection DNA immunization Foot-and-mouth disease virus Cellular immune response Serum neutralization Mouse model Vaccine Protection DNA immunization Foot-and-mouth disease virus Cellular immune response Serum neutralization Mouse model Borrego, B. Fernandez-Pacheco, P. Ganges, L. Domenech, N. Fernandez-Borges, N. Sobrino, F. Rodríguez, F. DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses |
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Despite foot-and-mouth disease virus (FMDV) being responsible for one of the most devastating animal diseases, little is known about the cellular immune mechanisms involved in protection against this virus. In this work we have studied the potential of DNA vaccines based on viral minigenes corresponding to three major B and T-cell FMDV epitopes (isolate C-S8c1) originally identified in natural hosts. The BTT epitopes [VP1 (133-156)-3A (11-40)-VP4 (20-34)] were cloned into the plasmid pCMV, either alone or fused to ubiquitin, the lysosomal targeting signal from LIMPII, a soluble version of CTLA4 or a signal peptide from the human prion protein, to analyze the effect of processing through different antigenic presentation pathways on the immunogenicity of the FMDV epitopes. As a first step in the analysis of modulation exerted by these target signals, a FMDV infection inhibition assay in Swiss outbred mice was developed and used to analyze the protection conferred by the different BTT-expressing plasmids. Only one of the 37 mice immunized with minigene-bearing plasmids developed specific neutralizing antibodies prior to FMDV challenge. As expected, this single mouse that had been immunized with the BTT tandem epitopes fused to a signal peptide (pCMV-spBTT) was protected against FMDV infection. Interestingly, nine more of the animals immunized with BTT-expressing plasmids did not show viremia at 48 h post-infection (pi), even in the absence of anti-FMDV antibodies prior to challenge. The highest protection (50%, six out of 12 mice) was observed with the plasmid expressing BTT alone, indicating that the targeting strategies used did not result in an improvement of the protection conferred by BTT epitopes. Interestingly, peptide specific CD4+ T-cells were detected for some of the BTT-protected mice. Thus, a DNA vaccine based on single FMDV B and T cell epitopes can protect mice, in the absence of specific antibodies at the time of challenge. Further work must be done to elucidate the mechanisms involved in protection and to determine the protective potential of these vaccines in natural FMDV hosts. © 2006 Elsevier Ltd. All rights reserved. |
format |
journal article |
topic_facet |
Vaccine Protection DNA immunization Foot-and-mouth disease virus Cellular immune response Serum neutralization Mouse model |
author |
Borrego, B. Fernandez-Pacheco, P. Ganges, L. Domenech, N. Fernandez-Borges, N. Sobrino, F. Rodríguez, F. |
author_facet |
Borrego, B. Fernandez-Pacheco, P. Ganges, L. Domenech, N. Fernandez-Borges, N. Sobrino, F. Rodríguez, F. |
author_sort |
Borrego, B. |
title |
DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses |
title_short |
DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses |
title_full |
DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses |
title_fullStr |
DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses |
title_full_unstemmed |
DNA vaccines expressing B and T cell epitopes can protect mice from FMDV infection in the absence of specific humoral responses |
title_sort |
dna vaccines expressing b and t cell epitopes can protect mice from fmdv infection in the absence of specific humoral responses |
publisher |
Elsevier |
publishDate |
2006 |
url |
http://hdl.handle.net/20.500.12792/4910 http://hdl.handle.net/10261/294811 |
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