Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein.
BACKGROUND: Modified Vaccinia Ankara (MVA) is an attenuated strain of Vaccinia virus (VACV) currently employed in many clinical trials against HIV/AIDS and other diseases. MVA still retains genes involved in host immune response evasion, enabling its optimization by removing some of them. The aim of...
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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/PMC3285208?pdf=render |
| _version_ | 1819162163130925056 |
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| author | Juliana Falivene María Paula Del Médico Zajac María Fernanda Pascutti Ana María Rodríguez Cynthia Maeto Beatriz Perdiguero Carmen E Gómez Mariano Esteban Gabriela Calamante María Magdalena Gherardi |
| author_facet | Juliana Falivene María Paula Del Médico Zajac María Fernanda Pascutti Ana María Rodríguez Cynthia Maeto Beatriz Perdiguero Carmen E Gómez Mariano Esteban Gabriela Calamante María Magdalena Gherardi |
| author_sort | Juliana Falivene |
| collection | DOAJ |
| description | BACKGROUND: Modified Vaccinia Ankara (MVA) is an attenuated strain of Vaccinia virus (VACV) currently employed in many clinical trials against HIV/AIDS and other diseases. MVA still retains genes involved in host immune response evasion, enabling its optimization by removing some of them. The aim of this study was to evaluate cellular immune responses (CIR) induced by an IL-18 binding protein gene (C12L) deleted vector (MVAΔC12L). METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were immunized with different doses of MVAΔC12L or MVA wild type (MVAwt), then CIR to VACV epitopes in immunogenic proteins were evaluated in spleen and draining lymph nodes at acute and memory phases (7 and 40 days post-immunization respectively). Compared with parental MVAwt, MVAΔC12L immunization induced a significant increase of two to three-fold in CD8(+) and CD4(+) T-cell responses to different VACV epitopes, with increased percentage of anti-VACV cytotoxic CD8(+) T-cells (CD107a/b(+)) during the acute phase of the response. Importantly, the immunogenicity enhancement was also observed after MVAΔC12L inoculation with different viral doses and by distinct routes (systemic and mucosal). Potentiation of MVA's CIR was also observed during the memory phase, in correlation with a higher protection against an intranasal challenge with VACV WR. Of note, we could also show a significant increase in the CIR against HIV antigens such as Env, Gag, Pol and Nef from different subtypes expressed from two recombinants of MVAΔC12L during heterologous DNA prime/MVA boost vaccination regimens. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the relevance of IL-18 bp contribution in the immune response evasion during MVA infection. Our findings clearly show that the deletion of the viral IL-18 bp gene is an effective approach to increase MVA vaccine efficacy, as immunogenicity improvements were observed against vector antigens and more importantly to HIV antigens. |
| first_indexed | 2024-12-22T17:23:52Z |
| format | Article |
| id | doaj.art-1bc24610786648a684aef0e331e57445 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T17:23:52Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1bc24610786648a684aef0e331e574452022-12-21T18:18:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0172e3222010.1371/journal.pone.0032220Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein.Juliana FaliveneMaría Paula Del Médico ZajacMaría Fernanda PascuttiAna María RodríguezCynthia MaetoBeatriz PerdigueroCarmen E GómezMariano EstebanGabriela CalamanteMaría Magdalena GherardiBACKGROUND: Modified Vaccinia Ankara (MVA) is an attenuated strain of Vaccinia virus (VACV) currently employed in many clinical trials against HIV/AIDS and other diseases. MVA still retains genes involved in host immune response evasion, enabling its optimization by removing some of them. The aim of this study was to evaluate cellular immune responses (CIR) induced by an IL-18 binding protein gene (C12L) deleted vector (MVAΔC12L). METHODOLOGY/PRINCIPAL FINDINGS: BALB/c and C57BL/6 mice were immunized with different doses of MVAΔC12L or MVA wild type (MVAwt), then CIR to VACV epitopes in immunogenic proteins were evaluated in spleen and draining lymph nodes at acute and memory phases (7 and 40 days post-immunization respectively). Compared with parental MVAwt, MVAΔC12L immunization induced a significant increase of two to three-fold in CD8(+) and CD4(+) T-cell responses to different VACV epitopes, with increased percentage of anti-VACV cytotoxic CD8(+) T-cells (CD107a/b(+)) during the acute phase of the response. Importantly, the immunogenicity enhancement was also observed after MVAΔC12L inoculation with different viral doses and by distinct routes (systemic and mucosal). Potentiation of MVA's CIR was also observed during the memory phase, in correlation with a higher protection against an intranasal challenge with VACV WR. Of note, we could also show a significant increase in the CIR against HIV antigens such as Env, Gag, Pol and Nef from different subtypes expressed from two recombinants of MVAΔC12L during heterologous DNA prime/MVA boost vaccination regimens. CONCLUSIONS/SIGNIFICANCE: This study demonstrates the relevance of IL-18 bp contribution in the immune response evasion during MVA infection. Our findings clearly show that the deletion of the viral IL-18 bp gene is an effective approach to increase MVA vaccine efficacy, as immunogenicity improvements were observed against vector antigens and more importantly to HIV antigens.http://europepmc.org/articles/PMC3285208?pdf=render |
| spellingShingle | Juliana Falivene María Paula Del Médico Zajac María Fernanda Pascutti Ana María Rodríguez Cynthia Maeto Beatriz Perdiguero Carmen E Gómez Mariano Esteban Gabriela Calamante María Magdalena Gherardi Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. PLoS ONE |
| title | Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. |
| title_full | Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. |
| title_fullStr | Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. |
| title_full_unstemmed | Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. |
| title_short | Improving the MVA vaccine potential by deleting the viral gene coding for the IL-18 binding protein. |
| title_sort | improving the mva vaccine potential by deleting the viral gene coding for the il 18 binding protein |
| url | http://europepmc.org/articles/PMC3285208?pdf=render |
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