Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors.
Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune res...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2011
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/f2fa053478d04f77baca2398b5125f5a |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:f2fa053478d04f77baca2398b5125f5a |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:f2fa053478d04f77baca2398b5125f5a2021-11-18T06:58:47ZImproved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors.1932-620310.1371/journal.pone.0016819https://doaj.org/article/f2fa053478d04f77baca2398b5125f5a2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347234/?tool=EBIhttps://doaj.org/toc/1932-6203Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines.Esther D QuakkelaarAnke RedekerElias K HaddadAlexandre HarariStella Mayo McCaugheyThomas DuhenAbdelali Filali-MouhimJean-Philippe GouletNikki M LoofFerry OssendorpBeatriz PerdigueroPaul HeinenCarmen E GomezKaren V KiblerDavid M KoelleRafick P SékalyFederica SallustoAntonio LanzavecchiaGiuseppe PantaleoMariano EstebanJim TartagliaBertram L JacobsCornelis J M MeliefPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 2, p e16819 (2011) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Esther D Quakkelaar Anke Redeker Elias K Haddad Alexandre Harari Stella Mayo McCaughey Thomas Duhen Abdelali Filali-Mouhim Jean-Philippe Goulet Nikki M Loof Ferry Ossendorp Beatriz Perdiguero Paul Heinen Carmen E Gomez Karen V Kibler David M Koelle Rafick P Sékaly Federica Sallusto Antonio Lanzavecchia Giuseppe Pantaleo Mariano Esteban Jim Tartaglia Bertram L Jacobs Cornelis J M Melief Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. |
| description |
Attenuated poxviruses are safe and capable of expressing foreign antigens. Poxviruses are applied in veterinary vaccination and explored as candidate vaccines for humans. However, poxviruses express multiple genes encoding proteins that interfere with components of the innate and adaptive immune response. This manuscript describes two strategies aimed to improve the immunogenicity of the highly attenuated, host-range restricted poxvirus NYVAC: deletion of the viral gene encoding type-I interferon-binding protein and development of attenuated replication-competent NYVAC. We evaluated these newly generated NYVAC mutants, encoding HIV-1 env, gag, pol and nef, for their ability to stimulate HIV-specific CD8 T-cell responses in vitro from blood mononuclear cells of HIV-infected subjects. The new vectors were evaluated and compared to the parental NYVAC vector in dendritic cells (DCs), RNA expression arrays, HIV gag expression and cross-presentation assays in vitro. Deletion of type-I interferon-binding protein enhanced expression of interferon and interferon-induced genes in DCs, and increased maturation of infected DCs. Restoration of replication competence induced activation of pathways involving antigen processing and presentation. Also, replication-competent NYVAC showed increased Gag expression in infected cells, permitting enhanced cross-presentation to HIV-specific CD8 T cells and proliferation of HIV-specific memory CD8 T-cells in vitro. The recombinant NYVAC combining both modifications induced interferon-induced genes and genes involved in antigen processing and presentation, as well as increased Gag expression. This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines. |
| format |
article |
| author |
Esther D Quakkelaar Anke Redeker Elias K Haddad Alexandre Harari Stella Mayo McCaughey Thomas Duhen Abdelali Filali-Mouhim Jean-Philippe Goulet Nikki M Loof Ferry Ossendorp Beatriz Perdiguero Paul Heinen Carmen E Gomez Karen V Kibler David M Koelle Rafick P Sékaly Federica Sallusto Antonio Lanzavecchia Giuseppe Pantaleo Mariano Esteban Jim Tartaglia Bertram L Jacobs Cornelis J M Melief |
| author_facet |
Esther D Quakkelaar Anke Redeker Elias K Haddad Alexandre Harari Stella Mayo McCaughey Thomas Duhen Abdelali Filali-Mouhim Jean-Philippe Goulet Nikki M Loof Ferry Ossendorp Beatriz Perdiguero Paul Heinen Carmen E Gomez Karen V Kibler David M Koelle Rafick P Sékaly Federica Sallusto Antonio Lanzavecchia Giuseppe Pantaleo Mariano Esteban Jim Tartaglia Bertram L Jacobs Cornelis J M Melief |
| author_sort |
Esther D Quakkelaar |
| title |
Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. |
| title_short |
Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. |
| title_full |
Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. |
| title_fullStr |
Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. |
| title_full_unstemmed |
Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors. |
| title_sort |
improved innate and adaptive immunostimulation by genetically modified hiv-1 protein expressing nyvac vectors. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2011 |
| url |
https://doaj.org/article/f2fa053478d04f77baca2398b5125f5a |
| work_keys_str_mv |
AT estherdquakkelaar improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT ankeredeker improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT eliaskhaddad improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT alexandreharari improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT stellamayomccaughey improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT thomasduhen improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT abdelalifilalimouhim improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT jeanphilippegoulet improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT nikkimloof improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT ferryossendorp improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT beatrizperdiguero improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT paulheinen improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT carmenegomez improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT karenvkibler improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT davidmkoelle improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT rafickpsekaly improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT federicasallusto improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT antoniolanzavecchia improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT giuseppepantaleo improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT marianoesteban improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT jimtartaglia improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT bertramljacobs improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors AT cornelisjmmelief improvedinnateandadaptiveimmunostimulationbygeneticallymodifiedhiv1proteinexpressingnyvacvectors |
| _version_ |
1718424143578267648 |