Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant
Autor(a) principal: | |
---|---|
Data de Publicação: | 2018 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Scientia Medica (Porto Alegre. Online) |
Texto Completo: | https://revistaseletronicas.pucrs.br/scientiamedica/article/view/30555 |
Resumo: | AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days.RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred.CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo. |
id |
PUC_RS-25_0ce0acc3597bfe729f0555f027aeea7c |
---|---|
oai_identifier_str |
oai:ojs.revistaseletronicas.pucrs.br:article/30555 |
network_acronym_str |
PUC_RS-25 |
network_name_str |
Scientia Medica (Porto Alegre. Online) |
repository_id_str |
|
spelling |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvantEvaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvantcellular immunityhuman papillomavirusoncogene proteininterleukin-18.imunidade celularpapiloma vírus humanoproteínas oncogênicasinterleucina-18.AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days.RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred.CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo.***Avaliação da potência terapêutica da vacina de DNA do papilomavírus humano-16 E7 isolada e com interleucina-18 como adjuvante genético***OBJETIVOS: Apesar da existência de vacinas preventivas eficazes contra o papilomavírus humano (HPV), são necessárias vacinas terapêuticas que desencadeiem respostas imunes mediadas por células para tratar infecções e malignidades estabelecidas. O objetivo deste estudo foi avaliar a potência terapêutica da vacina de ácido desoxirribonucleico (DNA) HPV-16 E7 isolada e com interleucina (IL)-18.MÉTODOS: Expressões in vitro de IL-18 foram realizadas em células renais embrionárias humanas 293 e confirmadas por Western blotting. A vacina de DNA foi disponibilizada em um estudo anterior. Um total de 45 camundongos fêmeas C57BL/6 divididos em cinco grupos (vacina de DNA, vacina de DNA adjuvada com IL-18, pcDNA3.1 e solução salina tamponada com fosfato) e foram inoculados com linhagem murina-1 de carcinoma relacionado ao HPV, expressando antígenos E6 / E7 do HPV-16. Os animais foram então imunizados por via subcutânea duas vezes no intervalo de sete dias. A imunidade antitumoral e antígeno-celular específica foi avaliada pela proliferação de linfócitos (ensaio de brometo de 3- [4,5-dimetiltiazol-2-il] -2,5-difeniltetrazólio: MTT), ensaio de liberação de lactato desidrogenase, ensaio de IL-4 e ensaio de interferon-gama [IFN-γ]. O tamanho do tumor foi seguido por 62 dias.RESULTADOS: O ensaio MTT, que mede a proliferação de linfócitos em resposta ao antígeno específico, aumentou nos grupos de coadministração e de vacina de DNA em comparação aos grupos controle e adjuvante genético (p <0,001). Os camundongos imunizados com a coadministração geraram significativamente mais IFN-γ e IL-4 do que os outros camundongos imunizados (p<0,001). A redução do tamanho do tumor nos grupos de coadministração e de vacina de DNA foi significativamente mais acentuada do que nos grupos controle e adjuvante genético (p<0,001), mas não houve nenhuma diferença estatisticamente significativa entre os grupos vacina de DNA e coadministração (p=0,15).CONCLUSÕES: A IL-18 como adjuvante genético e a vacina de DNA E7 aumentaram as respostas imunes em sistemas modelo de camundongos contra o câncer cervical. No entanto, o uso de IL-18 como adjuvante genético com a vacina de DNA E7 não teve efeito sinérgico significativo nas respostas imunes in vivo.Editora da PUCRS - ediPUCRS2018-08-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://revistaseletronicas.pucrs.br/scientiamedica/article/view/3055510.15448/1980-6108.2018.3.30555Scientia Medica; Vol. 28 No. 3 (2018); ID30555Scientia Medica; v. 28 n. 3 (2018); ID305551980-61081806-556210.15448/1980-6108.2018.3reponame:Scientia Medica (Porto Alegre. Online)instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)instacron:PUC_RSenghttps://revistaseletronicas.pucrs.br/scientiamedica/article/view/30555/17102Copyright (c) 2018 Scientia Medicahttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessPourhossein, BehzadGhaemi, AmirFazeli, MaryamAzadmanesh, KayhanMahmoodi, MahmoodMirshafiey, AbbasShahmahmoodi, Shohreh2018-10-17T21:53:12Zoai:ojs.revistaseletronicas.pucrs.br:article/30555Revistahttps://revistaseletronicas.pucrs.br/scientiamedica/PUBhttps://revistaseletronicas.pucrs.br/scientiamedica/oaiscientiamedica@pucrs.br || editora.periodicos@pucrs.br1980-61081806-5562opendoar:2018-10-17T21:53:12Scientia Medica (Porto Alegre. Online) - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS)false |
dc.title.none.fl_str_mv |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
title |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
spellingShingle |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant Pourhossein, Behzad cellular immunity human papillomavirus oncogene protein interleukin-18. imunidade celular papiloma vírus humano proteínas oncogênicas interleucina-18. |
title_short |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
title_full |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
title_fullStr |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
title_full_unstemmed |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
title_sort |
Evaluation of therapeutic potency of human papillomavirus-16 E7 DNA vaccine alone and with interleukin-18 as a genetic adjuvant |
author |
Pourhossein, Behzad |
author_facet |
Pourhossein, Behzad Ghaemi, Amir Fazeli, Maryam Azadmanesh, Kayhan Mahmoodi, Mahmood Mirshafiey, Abbas Shahmahmoodi, Shohreh |
author_role |
author |
author2 |
Ghaemi, Amir Fazeli, Maryam Azadmanesh, Kayhan Mahmoodi, Mahmood Mirshafiey, Abbas Shahmahmoodi, Shohreh |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Pourhossein, Behzad Ghaemi, Amir Fazeli, Maryam Azadmanesh, Kayhan Mahmoodi, Mahmood Mirshafiey, Abbas Shahmahmoodi, Shohreh |
dc.subject.por.fl_str_mv |
cellular immunity human papillomavirus oncogene protein interleukin-18. imunidade celular papiloma vírus humano proteínas oncogênicas interleucina-18. |
topic |
cellular immunity human papillomavirus oncogene protein interleukin-18. imunidade celular papiloma vírus humano proteínas oncogênicas interleucina-18. |
description |
AIMS: Despite the existence of effective preventive vaccines for human papillomavirus (HPV), therapeutic vaccines that trigger cell-mediated immune responses are required to treat established infections and malignancies. The aim of this study was to evaluate the therapeutic potency of HPV-16 E7 deoxyribonucleic acid (DNA) vaccine alone and with interleukin (IL)-18. METHODS: In vitro expressions of IL-18 were performed on human embryonic kidney 293 cells and confirmed it by Western blotting methods. DNA vaccine was available from a previous study. A total of 45 female C57BL/6 mice divided into five groups (DNA vaccine, DNA vaccine adjuvanted with IL-18, pcDNA3.1, and phosphate buffer saline) were inoculated with murine tissue culture-1 cell line of HPV related carcinoma, expressing HPV-16 E6/E7 antigens. They were then immunized subcutaneously twice at a seven-day interval. The antitumor and antigen specific-cellular immunity were assessed by lymphocyte proliferation (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide: MTT) assay, lactate dehydrogenase release assay, IL-4 assay and interferon-gamma (IFN-γ) assay. Tumor size was followed for 62 days.RESULTS: MTT assay, which measures the lymphocyte proliferation in response to the specific antigen, increased in the co-administration and the DNA vaccine groups as compared to control and genetic adjuvant groups (p<0.001). The mice immunized with the co-administration generated significantly more IFN-γ and IL-4 than other immunized mice (p<0.001). Reduction of the tumor size in the co-administration and the DNA vaccine groups was significantly more pronounced than in the control and genetic adjuvant groups (p<0.001), but no statistically significant difference between DNA vaccine and co-administration groups (p=0.15) occurred.CONCLUSIONS: IL-18 as a genetic adjuvant and E7 DNA vaccine alone enhanced immune responses in mouse model systems against cervical cancer. However, using of IL-18 as a genetic adjuvant with E7 DNA vaccine had no significant synergistic effect on the immune responses in vivo. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-08-03 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://revistaseletronicas.pucrs.br/scientiamedica/article/view/30555 10.15448/1980-6108.2018.3.30555 |
url |
https://revistaseletronicas.pucrs.br/scientiamedica/article/view/30555 |
identifier_str_mv |
10.15448/1980-6108.2018.3.30555 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://revistaseletronicas.pucrs.br/scientiamedica/article/view/30555/17102 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2018 Scientia Medica https://creativecommons.org/licenses/by/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2018 Scientia Medica https://creativecommons.org/licenses/by/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Editora da PUCRS - ediPUCRS |
publisher.none.fl_str_mv |
Editora da PUCRS - ediPUCRS |
dc.source.none.fl_str_mv |
Scientia Medica; Vol. 28 No. 3 (2018); ID30555 Scientia Medica; v. 28 n. 3 (2018); ID30555 1980-6108 1806-5562 10.15448/1980-6108.2018.3 reponame:Scientia Medica (Porto Alegre. Online) instname:Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) instacron:PUC_RS |
instname_str |
Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
instacron_str |
PUC_RS |
institution |
PUC_RS |
reponame_str |
Scientia Medica (Porto Alegre. Online) |
collection |
Scientia Medica (Porto Alegre. Online) |
repository.name.fl_str_mv |
Scientia Medica (Porto Alegre. Online) - Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS) |
repository.mail.fl_str_mv |
scientiamedica@pucrs.br || editora.periodicos@pucrs.br |
_version_ |
1809101751875272704 |