A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants.
Lumazine synthase from Brucella spp. (BLS) is a highly immunogenic decameric protein. It is possible to insert foreign peptides or proteins at its ten-amino acid termini. These chimeras elicit systemic and oral immunity without adjuvants, which are commonly needed in the formulation of subunit-based...
| 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/PMC3454435?pdf=render |
| _version_ | 1819236457218310144 |
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| author | Paula M Berguer Vanina A Alzogaray Andrés Hugo Rossi Juliana Mundiñano Isabel Piazzon Fernando A Goldbaum |
| author_facet | Paula M Berguer Vanina A Alzogaray Andrés Hugo Rossi Juliana Mundiñano Isabel Piazzon Fernando A Goldbaum |
| author_sort | Paula M Berguer |
| collection | DOAJ |
| description | Lumazine synthase from Brucella spp. (BLS) is a highly immunogenic decameric protein. It is possible to insert foreign peptides or proteins at its ten-amino acid termini. These chimeras elicit systemic and oral immunity without adjuvants, which are commonly needed in the formulation of subunit-based vaccines. Here, we show that BLS induces the cross presentation of a covalently attached peptide OVA(257-264) and a specific cytotoxic response to this peptide in the absence of adjuvants. Unlike other subunit-based vaccines, this chimera induces rapid activation of CTLs and a specific cytotoxic response, making this polymeric protein an ideal antigen carrier for vaccine development. Adoptive transfer of transgenic OT-I T cells revealed efficient cross presentation of BLS-OVA(257-264)in vivo. BLS-OVA(257-264) immunization induced the proliferation of OVA(257-264)-specific CD8+ lymphocytes and also increased the percentage of OVA(257-264)-specific CD8+ cells expressing the early activation marker CD69; after 5 days, the percentage of OVA(257-264)-specific CD8+ cells expressing high levels of CD44 increased. This cell subpopulation showed decreased expression of IL-7Rα, indicating that BLS-OVA(257-264) induced the generation of CD8+ effector cells. BLS-OVA(257-264) was cross presented in vitro independently of the presence of a functional TLR4 in the DCs. Finally, we show that immunization of wild type mice with the chimera BLS-OVA(257-264) without adjuvants induced a strong OVA(257-264)-specific effector cytotoxic response. This cytotoxicity is dependent on TLR4 as is not induced in mice lacking a functional receptor. These data show that TLR4 signaling is necessary for the induction of a cytotoxic response but not for antigen cross presentation. |
| first_indexed | 2024-12-23T13:04:44Z |
| format | Article |
| id | doaj.art-65ff7c58e58e402bb16bca667af6aa7b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T13:04:44Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-65ff7c58e58e402bb16bca667af6aa7b2022-12-21T17:45:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0179e4570510.1371/journal.pone.0045705A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants.Paula M BerguerVanina A AlzogarayAndrés Hugo RossiJuliana MundiñanoIsabel PiazzonFernando A GoldbaumLumazine synthase from Brucella spp. (BLS) is a highly immunogenic decameric protein. It is possible to insert foreign peptides or proteins at its ten-amino acid termini. These chimeras elicit systemic and oral immunity without adjuvants, which are commonly needed in the formulation of subunit-based vaccines. Here, we show that BLS induces the cross presentation of a covalently attached peptide OVA(257-264) and a specific cytotoxic response to this peptide in the absence of adjuvants. Unlike other subunit-based vaccines, this chimera induces rapid activation of CTLs and a specific cytotoxic response, making this polymeric protein an ideal antigen carrier for vaccine development. Adoptive transfer of transgenic OT-I T cells revealed efficient cross presentation of BLS-OVA(257-264)in vivo. BLS-OVA(257-264) immunization induced the proliferation of OVA(257-264)-specific CD8+ lymphocytes and also increased the percentage of OVA(257-264)-specific CD8+ cells expressing the early activation marker CD69; after 5 days, the percentage of OVA(257-264)-specific CD8+ cells expressing high levels of CD44 increased. This cell subpopulation showed decreased expression of IL-7Rα, indicating that BLS-OVA(257-264) induced the generation of CD8+ effector cells. BLS-OVA(257-264) was cross presented in vitro independently of the presence of a functional TLR4 in the DCs. Finally, we show that immunization of wild type mice with the chimera BLS-OVA(257-264) without adjuvants induced a strong OVA(257-264)-specific effector cytotoxic response. This cytotoxicity is dependent on TLR4 as is not induced in mice lacking a functional receptor. These data show that TLR4 signaling is necessary for the induction of a cytotoxic response but not for antigen cross presentation.http://europepmc.org/articles/PMC3454435?pdf=render |
| spellingShingle | Paula M Berguer Vanina A Alzogaray Andrés Hugo Rossi Juliana Mundiñano Isabel Piazzon Fernando A Goldbaum A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants. PLoS ONE |
| title | A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants. |
| title_full | A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants. |
| title_fullStr | A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants. |
| title_full_unstemmed | A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants. |
| title_short | A polymeric protein induces specific cytotoxicity in a TLR4 dependent manner in the absence of adjuvants. |
| title_sort | polymeric protein induces specific cytotoxicity in a tlr4 dependent manner in the absence of adjuvants |
| url | http://europepmc.org/articles/PMC3454435?pdf=render |
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