A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines
Signal sequences (ss) play a critical role in the sorting of nascent secretory and membrane proteins. This function has been conserved from bacteria through eukaryotes, although ss appear diverse in length and amino acid composition. Sorting of proteins is also critical to instruct antigens for a pr...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-02-01
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| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/21645515.2017.1264766 |
| _version_ | 1827807643530428416 |
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| author | Silvia Massa Francesca Paolini Gianfranca Curzio Marcelo Nazario Cordeiro Elena Illiano Olivia Costantina Demurtas Rosella Franconi Aldo Venuti |
| author_facet | Silvia Massa Francesca Paolini Gianfranca Curzio Marcelo Nazario Cordeiro Elena Illiano Olivia Costantina Demurtas Rosella Franconi Aldo Venuti |
| author_sort | Silvia Massa |
| collection | DOAJ |
| description | Signal sequences (ss) play a critical role in the sorting of nascent secretory and membrane proteins. This function has been conserved from bacteria through eukaryotes, although ss appear diverse in length and amino acid composition. Sorting of proteins is also critical to instruct antigens for a proper immunological response. Thus, a plant ss was used to drive Human Papillomavirus (HPV) model antigens into the human secretory pathway: the HPV16 E7 oncoprotein, its chimera with the coat protein (CP) of the Potato Virus X (PVX), the first 200 amino acids of the HPV16 minor capsid protein L2 (known to harbour cross-reacting epitopes) and its chimera with E7 gene. These genes were used to transfect HEK-293 cells and to immunize C57BL/6 mice. The ss-provided genes were expressed, and proteins detected by immunofluorescence and immunoblotting. Mouse immunization with DNA constructs carrying the ss elicited a strong humoral response against both E7 and L2 and a weak cell-mediated immunity. To our knowledge this is the first demonstration that a signal sequence derived from a plant can modulate the sorting of a heterologous protein in mammalian cells. This activity in mammalian cells may be responsible for the observed increased humoral response to DNA-based vaccines that are generally weak inducers of IgG response. This might open new perspectives in the design of DNA vaccines, especially to counteract infections where a strong humoral response is needed. |
| first_indexed | 2024-03-11T22:00:19Z |
| format | Article |
| id | doaj.art-1087a815764a42019357b2af89f36d6d |
| institution | Directory Open Access Journal |
| issn | 2164-5515 2164-554X |
| language | English |
| last_indexed | 2024-03-11T22:00:19Z |
| publishDate | 2017-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj.art-1087a815764a42019357b2af89f36d6d2023-09-25T11:02:54ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2017-02-0113227128210.1080/21645515.2017.12647661264766A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccinesSilvia Massa0Francesca Paolini1Gianfranca Curzio2Marcelo Nazario Cordeiro3Elena Illiano4Olivia Costantina Demurtas5Rosella Franconi6Aldo Venuti7ENEA - Italian National Agency for New Technologies, Energy and the EnvironmentRegina Elena National Cancer Institute HPV-UNITRegina Elena National Cancer Institute HPV-UNITFederal University of Pernambuco, LEMTEUniversity of MilanENEA - Italian National Agency for New Technologies, Energy and the EnvironmentLaboratory of Biomedical TechnologiesRegina Elena National Cancer Institute HPV-UNITSignal sequences (ss) play a critical role in the sorting of nascent secretory and membrane proteins. This function has been conserved from bacteria through eukaryotes, although ss appear diverse in length and amino acid composition. Sorting of proteins is also critical to instruct antigens for a proper immunological response. Thus, a plant ss was used to drive Human Papillomavirus (HPV) model antigens into the human secretory pathway: the HPV16 E7 oncoprotein, its chimera with the coat protein (CP) of the Potato Virus X (PVX), the first 200 amino acids of the HPV16 minor capsid protein L2 (known to harbour cross-reacting epitopes) and its chimera with E7 gene. These genes were used to transfect HEK-293 cells and to immunize C57BL/6 mice. The ss-provided genes were expressed, and proteins detected by immunofluorescence and immunoblotting. Mouse immunization with DNA constructs carrying the ss elicited a strong humoral response against both E7 and L2 and a weak cell-mediated immunity. To our knowledge this is the first demonstration that a signal sequence derived from a plant can modulate the sorting of a heterologous protein in mammalian cells. This activity in mammalian cells may be responsible for the observed increased humoral response to DNA-based vaccines that are generally weak inducers of IgG response. This might open new perspectives in the design of DNA vaccines, especially to counteract infections where a strong humoral response is needed.http://dx.doi.org/10.1080/21645515.2017.1264766humoral immune responsehpvinfectious diseasesplant signal sequencesvaccines |
| spellingShingle | Silvia Massa Francesca Paolini Gianfranca Curzio Marcelo Nazario Cordeiro Elena Illiano Olivia Costantina Demurtas Rosella Franconi Aldo Venuti A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines Human Vaccines & Immunotherapeutics humoral immune response hpv infectious diseases plant signal sequences vaccines |
| title | A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines |
| title_full | A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines |
| title_fullStr | A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines |
| title_full_unstemmed | A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines |
| title_short | A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines |
| title_sort | plant protein signal sequence improved humoral immune response to hpv prophylactic and therapeutic dna vaccines |
| topic | humoral immune response hpv infectious diseases plant signal sequences vaccines |
| url | http://dx.doi.org/10.1080/21645515.2017.1264766 |
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