A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus.
There is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleopr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3187825?pdf=render |
| _version_ | 1818902263256580096 |
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| author | Alan G Goodman Paul P Heinen Susana Guerra Aneesh Vijayan Carlos Oscar S Sorzano Carmen E Gomez Mariano Esteban |
| author_facet | Alan G Goodman Paul P Heinen Susana Guerra Aneesh Vijayan Carlos Oscar S Sorzano Carmen E Gomez Mariano Esteban |
| author_sort | Alan G Goodman |
| collection | DOAJ |
| description | There is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleoproteins, rather than the surface hemagglutinin and neuraminidase proteins. In addition, non-disease-causing viral vectors are a popular choice as a delivery system for the influenza virus antigens. As a proof-of-concept, we have designed a novel influenza virus immunogen based on the NP backbone containing human T cell epitopes for M1, NS1, NP, PB1 and PA proteins (referred as NPmix) as well as a construct containing the conserved regions of influenza virus neuraminidase (N-terminal) and hemagglutinin (C-terminal) (referred as NA-HA). DNA vectors and vaccinia virus recombinants expressing NPmix (WR-NP) or both NPmix plus NA-HA (WR-flu) in the cytosol were tested in a heterologous DNA-prime/vaccinia virus-boost vaccine regimen in mice. We observed an increase in the number of influenza virus-specific IFNγ-secreting splenocytes, composed of populations marked by CD4(+) and CD8(+) T cells producing IFNγ or TNFα. Upon challenge with influenza virus, the vaccinated mice exhibited decreased viral load in the lungs and a delay in mortality. These findings suggest that DNA prime/poxvirus boost with human multi-epitope recombinant influenza virus proteins is a valid approach for a general T-cell vaccine to protect against influenza virus infection. |
| first_indexed | 2024-12-19T20:32:52Z |
| format | Article |
| id | doaj.art-8719081f2643411f8d187738fc19a7fd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T20:32:52Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-8719081f2643411f8d187738fc19a7fd2022-12-21T20:06:37ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01610e2593810.1371/journal.pone.0025938A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus.Alan G GoodmanPaul P HeinenSusana GuerraAneesh VijayanCarlos Oscar S SorzanoCarmen E GomezMariano EstebanThere is a need to develop a universal vaccine against influenza virus infection to avoid developing new formulations of a seasonal vaccine each year. Many of the vaccine strategies for a universal vaccine target strain-conserved influenza virus proteins, such as the matrix, polymerase, and nucleoproteins, rather than the surface hemagglutinin and neuraminidase proteins. In addition, non-disease-causing viral vectors are a popular choice as a delivery system for the influenza virus antigens. As a proof-of-concept, we have designed a novel influenza virus immunogen based on the NP backbone containing human T cell epitopes for M1, NS1, NP, PB1 and PA proteins (referred as NPmix) as well as a construct containing the conserved regions of influenza virus neuraminidase (N-terminal) and hemagglutinin (C-terminal) (referred as NA-HA). DNA vectors and vaccinia virus recombinants expressing NPmix (WR-NP) or both NPmix plus NA-HA (WR-flu) in the cytosol were tested in a heterologous DNA-prime/vaccinia virus-boost vaccine regimen in mice. We observed an increase in the number of influenza virus-specific IFNγ-secreting splenocytes, composed of populations marked by CD4(+) and CD8(+) T cells producing IFNγ or TNFα. Upon challenge with influenza virus, the vaccinated mice exhibited decreased viral load in the lungs and a delay in mortality. These findings suggest that DNA prime/poxvirus boost with human multi-epitope recombinant influenza virus proteins is a valid approach for a general T-cell vaccine to protect against influenza virus infection.http://europepmc.org/articles/PMC3187825?pdf=render |
| spellingShingle | Alan G Goodman Paul P Heinen Susana Guerra Aneesh Vijayan Carlos Oscar S Sorzano Carmen E Gomez Mariano Esteban A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus. PLoS ONE |
| title | A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus. |
| title_full | A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus. |
| title_fullStr | A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus. |
| title_full_unstemmed | A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus. |
| title_short | A human multi-epitope recombinant vaccinia virus as a universal T cell vaccine candidate against influenza virus. |
| title_sort | human multi epitope recombinant vaccinia virus as a universal t cell vaccine candidate against influenza virus |
| url | http://europepmc.org/articles/PMC3187825?pdf=render |
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