DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies.
The lack of available vaccines against African swine fever virus (ASFV) means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA) to p54 and p30, two immunodominant structural viral antigens, exponential...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3458849?pdf=render |
| _version_ | 1818364051539886080 |
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| author | Jordi M Argilaguet Eva Pérez-Martín Miquel Nofrarías Carmina Gallardo Francesc Accensi Anna Lacasta Mercedes Mora Maria Ballester Ivan Galindo-Cardiel Sergio López-Soria José M Escribano Pedro A Reche Fernando Rodríguez |
| author_facet | Jordi M Argilaguet Eva Pérez-Martín Miquel Nofrarías Carmina Gallardo Francesc Accensi Anna Lacasta Mercedes Mora Maria Ballester Ivan Galindo-Cardiel Sergio López-Soria José M Escribano Pedro A Reche Fernando Rodríguez |
| author_sort | Jordi M Argilaguet |
| collection | DOAJ |
| description | The lack of available vaccines against African swine fever virus (ASFV) means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA) to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization. However, immunization with the resulting plasmid (pCMV-sHAPQ) did not confer protection against lethal challenge with the virulent E75 ASFV-strain. Due to the fact that CD8(+) T-cell responses are emerging as key components for ASFV protection, we designed a new plasmid construct, pCMV-UbsHAPQ, encoding the three viral determinants above mentioned (sHA, p54 and p30) fused to ubiquitin, aiming to improve Class I antigen presentation and to enhance the CTL responses induced. As expected, immunization with pCMV-UbsHAPQ induced specific T-cell responses in the absence of antibodies and, more important, protected a proportion of immunized-pigs from lethal challenge with ASFV. In contrast with control pigs, survivor animals showed a peak of CD8(+) T-cells at day 3 post-infection, coinciding with the absence of viremia at this time point. Finally, an in silico prediction of CTL peptides has allowed the identification of two SLA I-restricted 9-mer peptides within the hemagglutinin of the virus, capable of in vitro stimulating the specific secretion of IFNγ when using PBMCs from survivor pigs. Our results confirm the relevance of T-cell responses in protection against ASF and open new expectations for the future development of more efficient recombinant vaccines against this disease. |
| first_indexed | 2024-12-13T21:58:13Z |
| format | Article |
| id | doaj.art-ff9f0a0ee55543a6a8e7739ce0242728 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T21:58:13Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ff9f0a0ee55543a6a8e7739ce02427282022-12-21T23:30:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4094210.1371/journal.pone.0040942DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies.Jordi M ArgilaguetEva Pérez-MartínMiquel NofraríasCarmina GallardoFrancesc AccensiAnna LacastaMercedes MoraMaria BallesterIvan Galindo-CardielSergio López-SoriaJosé M EscribanoPedro A RecheFernando RodríguezThe lack of available vaccines against African swine fever virus (ASFV) means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA) to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization. However, immunization with the resulting plasmid (pCMV-sHAPQ) did not confer protection against lethal challenge with the virulent E75 ASFV-strain. Due to the fact that CD8(+) T-cell responses are emerging as key components for ASFV protection, we designed a new plasmid construct, pCMV-UbsHAPQ, encoding the three viral determinants above mentioned (sHA, p54 and p30) fused to ubiquitin, aiming to improve Class I antigen presentation and to enhance the CTL responses induced. As expected, immunization with pCMV-UbsHAPQ induced specific T-cell responses in the absence of antibodies and, more important, protected a proportion of immunized-pigs from lethal challenge with ASFV. In contrast with control pigs, survivor animals showed a peak of CD8(+) T-cells at day 3 post-infection, coinciding with the absence of viremia at this time point. Finally, an in silico prediction of CTL peptides has allowed the identification of two SLA I-restricted 9-mer peptides within the hemagglutinin of the virus, capable of in vitro stimulating the specific secretion of IFNγ when using PBMCs from survivor pigs. Our results confirm the relevance of T-cell responses in protection against ASF and open new expectations for the future development of more efficient recombinant vaccines against this disease.http://europepmc.org/articles/PMC3458849?pdf=render |
| spellingShingle | Jordi M Argilaguet Eva Pérez-Martín Miquel Nofrarías Carmina Gallardo Francesc Accensi Anna Lacasta Mercedes Mora Maria Ballester Ivan Galindo-Cardiel Sergio López-Soria José M Escribano Pedro A Reche Fernando Rodríguez DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. PLoS ONE |
| title | DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. |
| title_full | DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. |
| title_fullStr | DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. |
| title_full_unstemmed | DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. |
| title_short | DNA vaccination partially protects against African swine fever virus lethal challenge in the absence of antibodies. |
| title_sort | dna vaccination partially protects against african swine fever virus lethal challenge in the absence of antibodies |
| url | http://europepmc.org/articles/PMC3458849?pdf=render |
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