Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome
Autor(a) principal: | |
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Data de Publicação: | 2011 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/33560 http://dx.doi.org/10.1186/1743-422X-8-127 |
Resumo: | Background: the attenuated Yellow fever (YF) 17D vaccine virus is one of the safest and most effective viral vaccines administered to humans, in which it elicits a polyvalent immune response. Herein, we used the YF 17D backbone to express a Trypanosoma cruzi CD8(+) T cell epitope from the Amastigote Surface Protein 2 (ASP-2) to provide further evidence for the potential of this virus to express foreign epitopes. the TEWETGQI CD8(+) T cell epitope was cloned and expressed based on two different genomic insertion sites: in the fg loop of the viral Envelope protein and the protease cleavage site between the NS2B and NS3. We investigated whether the site of expression had any influence on immunogenicity of this model epitope.Results: Recombinant viruses replicated similarly to vaccine virus YF 17D in cell culture and remained genetically stable after several serial passages in Vero cells. Immunogenicity studies revealed that both recombinant viruses elicited neutralizing antibodies to the YF virus as well as generated an antigen-specific gamma interferon mediated T-cell response in immunized mice. the recombinant viruses displayed a more attenuated phenotype than the YF 17DD vaccine counterpart in mice. Vaccination of a mouse lineage highly susceptible to infection by T. cruzi with a homologous prime-boost regimen of recombinant YF viruses elicited TEWETGQI specific CD8(+) T cells which might be correlated with a delay in mouse mortality after a challenge with a lethal dose of T. cruzi.Conclusions: We conclude that the YF 17D platform is useful to express T. cruzi (Protozoan) antigens at different functional regions of its genome with minimal reduction of vector fitness. in addition, the model T. cruzi epitope expressed at different regions of the YF 17D genome elicited a similar T cell-based immune response, suggesting that both expression sites are useful. However, the epitope as such is not protective and it remains to be seen whether expression of larger domains of ASP-2, which include the TEWETGQI epitope, will elicit better T-CD8+ responses to the latter. It is likely that additional antigens and recombinant virus formulations will be necessary to generate a protective response. |
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Nogueira, Raquel T.Nogueira, Alanderson R.Pereira, Mirian C. S.Rodrigues, Mauricio Martins [UNIFESP]Galler, RicardoBonaldo, Myrna C.Fundacao Oswaldo CruzUniversidade Federal de São Paulo (UNIFESP)2016-01-24T14:06:18Z2016-01-24T14:06:18Z2011-03-18Virology Journal. London: Biomed Central Ltd, v. 8, 13 p., 2011.1743-422Xhttp://repositorio.unifesp.br/handle/11600/33560http://dx.doi.org/10.1186/1743-422X-8-127WOS000288912600001.pdf10.1186/1743-422X-8-127WOS:000288912600001Background: the attenuated Yellow fever (YF) 17D vaccine virus is one of the safest and most effective viral vaccines administered to humans, in which it elicits a polyvalent immune response. Herein, we used the YF 17D backbone to express a Trypanosoma cruzi CD8(+) T cell epitope from the Amastigote Surface Protein 2 (ASP-2) to provide further evidence for the potential of this virus to express foreign epitopes. the TEWETGQI CD8(+) T cell epitope was cloned and expressed based on two different genomic insertion sites: in the fg loop of the viral Envelope protein and the protease cleavage site between the NS2B and NS3. We investigated whether the site of expression had any influence on immunogenicity of this model epitope.Results: Recombinant viruses replicated similarly to vaccine virus YF 17D in cell culture and remained genetically stable after several serial passages in Vero cells. Immunogenicity studies revealed that both recombinant viruses elicited neutralizing antibodies to the YF virus as well as generated an antigen-specific gamma interferon mediated T-cell response in immunized mice. the recombinant viruses displayed a more attenuated phenotype than the YF 17DD vaccine counterpart in mice. Vaccination of a mouse lineage highly susceptible to infection by T. cruzi with a homologous prime-boost regimen of recombinant YF viruses elicited TEWETGQI specific CD8(+) T cells which might be correlated with a delay in mouse mortality after a challenge with a lethal dose of T. cruzi.Conclusions: We conclude that the YF 17D platform is useful to express T. cruzi (Protozoan) antigens at different functional regions of its genome with minimal reduction of vector fitness. in addition, the model T. cruzi epitope expressed at different regions of the YF 17D genome elicited a similar T cell-based immune response, suggesting that both expression sites are useful. However, the epitope as such is not protective and it remains to be seen whether expression of larger domains of ASP-2, which include the TEWETGQI epitope, will elicit better T-CD8+ responses to the latter. It is likely that additional antigens and recombinant virus formulations will be necessary to generate a protective response.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Millennium Institute for Vaccine Development and TechnologyMillennium Institute for Gene Therapy (Brazil)Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Biol Mol Flavivirus, BR-21045900 Rio de Janeiro, BrazilFundacao Oswaldo Cruz, Inst Tecnol Imunobiol, BR-21045900 Rio de Janeiro, BrazilFundacao Oswaldo Cruz, Inst Oswaldo Cruz, Lab Ultraestrutura Celular, BR-21045900 Rio de Janeiro, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Terapia Celular Mol CTCMol, BR-04044010 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Terapia Celular Mol CTCMol, BR-04044010 São Paulo, BrazilMillennium Institute for Vaccine Development and Technology: CNPq - 420067/2005-1Web of Science13engBiomed Central LtdVirology JournalBiological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genomeinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000288912600001.pdfapplication/pdf2274665${dspace.ui.url}/bitstream/11600/33560/1/WOS000288912600001.pdfeb343e206c572a1cfa00e75a66621bd3MD51open accessTEXTWOS000288912600001.pdf.txtWOS000288912600001.pdf.txtExtracted texttext/plain65303${dspace.ui.url}/bitstream/11600/33560/2/WOS000288912600001.pdf.txt3f1ef55fd7a684ffb533dad022bcde53MD52open access11600/335602022-11-04 15:08:30.597open accessoai:repositorio.unifesp.br:11600/33560Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:28:56.754591Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
title |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
spellingShingle |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome Nogueira, Raquel T. |
title_short |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
title_full |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
title_fullStr |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
title_full_unstemmed |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
title_sort |
Biological and immunological characterization of recombinant Yellow Fever 17D Viruses expressing a Trypanosoma cruzi Amastigote Surface Protein-2 CD8(+) T cell epitope at two distinct regions of the genome |
author |
Nogueira, Raquel T. |
author_facet |
Nogueira, Raquel T. Nogueira, Alanderson R. Pereira, Mirian C. S. Rodrigues, Mauricio Martins [UNIFESP] Galler, Ricardo Bonaldo, Myrna C. |
author_role |
author |
author2 |
Nogueira, Alanderson R. Pereira, Mirian C. S. Rodrigues, Mauricio Martins [UNIFESP] Galler, Ricardo Bonaldo, Myrna C. |
author2_role |
author author author author author |
dc.contributor.institution.none.fl_str_mv |
Fundacao Oswaldo Cruz Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Nogueira, Raquel T. Nogueira, Alanderson R. Pereira, Mirian C. S. Rodrigues, Mauricio Martins [UNIFESP] Galler, Ricardo Bonaldo, Myrna C. |
description |
Background: the attenuated Yellow fever (YF) 17D vaccine virus is one of the safest and most effective viral vaccines administered to humans, in which it elicits a polyvalent immune response. Herein, we used the YF 17D backbone to express a Trypanosoma cruzi CD8(+) T cell epitope from the Amastigote Surface Protein 2 (ASP-2) to provide further evidence for the potential of this virus to express foreign epitopes. the TEWETGQI CD8(+) T cell epitope was cloned and expressed based on two different genomic insertion sites: in the fg loop of the viral Envelope protein and the protease cleavage site between the NS2B and NS3. We investigated whether the site of expression had any influence on immunogenicity of this model epitope.Results: Recombinant viruses replicated similarly to vaccine virus YF 17D in cell culture and remained genetically stable after several serial passages in Vero cells. Immunogenicity studies revealed that both recombinant viruses elicited neutralizing antibodies to the YF virus as well as generated an antigen-specific gamma interferon mediated T-cell response in immunized mice. the recombinant viruses displayed a more attenuated phenotype than the YF 17DD vaccine counterpart in mice. Vaccination of a mouse lineage highly susceptible to infection by T. cruzi with a homologous prime-boost regimen of recombinant YF viruses elicited TEWETGQI specific CD8(+) T cells which might be correlated with a delay in mouse mortality after a challenge with a lethal dose of T. cruzi.Conclusions: We conclude that the YF 17D platform is useful to express T. cruzi (Protozoan) antigens at different functional regions of its genome with minimal reduction of vector fitness. in addition, the model T. cruzi epitope expressed at different regions of the YF 17D genome elicited a similar T cell-based immune response, suggesting that both expression sites are useful. However, the epitope as such is not protective and it remains to be seen whether expression of larger domains of ASP-2, which include the TEWETGQI epitope, will elicit better T-CD8+ responses to the latter. It is likely that additional antigens and recombinant virus formulations will be necessary to generate a protective response. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-03-18 |
dc.date.accessioned.fl_str_mv |
2016-01-24T14:06:18Z |
dc.date.available.fl_str_mv |
2016-01-24T14:06:18Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Virology Journal. London: Biomed Central Ltd, v. 8, 13 p., 2011. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/33560 http://dx.doi.org/10.1186/1743-422X-8-127 |
dc.identifier.issn.none.fl_str_mv |
1743-422X |
dc.identifier.file.none.fl_str_mv |
WOS000288912600001.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/1743-422X-8-127 |
dc.identifier.wos.none.fl_str_mv |
WOS:000288912600001 |
identifier_str_mv |
Virology Journal. London: Biomed Central Ltd, v. 8, 13 p., 2011. 1743-422X WOS000288912600001.pdf 10.1186/1743-422X-8-127 WOS:000288912600001 |
url |
http://repositorio.unifesp.br/handle/11600/33560 http://dx.doi.org/10.1186/1743-422X-8-127 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
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Virology Journal |
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info:eu-repo/semantics/openAccess |
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openAccess |
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13 |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd |
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Biomed Central Ltd |
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