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[PMID]:28468915
[Au] Autor:Mei Y; Zhao L; Liu Y; Gong H; Song Y; Lei L; Zhu Y; Jin Z; Ma S; Hu B; Sun Q; Liu H
[Ad] Endereço:Institute of Blood and Marrow Transplantation, Department of Hematology, Collaborative Innovation Center of Hematology, the First Affiliated Hospital of Soochow University, Suzhou, P.R. China.
[Ti] Título:Combining DNA Vaccine and AIDA-1 in Attenuated Activates Tumor-Specific CD4 and CD8 T-cell Responses.
[So] Source:Cancer Immunol Res;5(6):503-514, 2017 Jun.
[Is] ISSN:2326-6074
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Stimulation of tumor-specific responses in both CD4 and CD8 T cells has been a challenge for effective tumor vaccines. We designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the tumor vaccine. The vaccine activated tumor-specific CD4 and CD8 T-cell responses, with increased T-cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. CD4 or CD8 T-cell depletion resulted in the loss of antitumor activity of the tumor vaccine, suggesting that the efficacy of the vaccine was dependent on both CD4 and CD8 T cells. Lung metastasis of the tumor was also inhibited by vaccine treatment. Similarly, the percentages of tumor-specific Th1 cytokine production by CD4 and CD8 T cells in the spleen, tumor, and bronchoalveolar lavage were increased after vaccine treatment. Tumor-specific proliferation of CD4 and CD8 T cells was also promoted by the vaccine. Tetramer staining and cytotoxicity assay showed enhanced tumor-specific CD8 T-cell response after vaccine treatment. Therefore, the tumor vaccine could activate both tumor-specific CD4 and CD8 T-cell responses. This vaccine strategy may be widely applicable to the development of oral or nasal vaccines against tumors. .
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Vacinas Anticâncer/administração & dosagem
Neoplasias/imunologia
Salmonella
Vacinas de DNA/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Proteínas de Transporte
Linhagem Celular Tumoral
Feminino
Camundongos Endogâmicos C57BL
Neoplasias/patologia
Neoplasias/terapia
Salmonella/genética
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ANKS1B protein, human); 0 (Cancer Vaccines); 0 (Carrier Proteins); 0 (Vaccines, DNA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1158/2326-6066.CIR-16-0240-T


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[PMID]:28459057
[Au] Autor:Koroleva EA; Kobets NV; Shcherbinin DN; Zigangirova NA; Shmarov MM; Tukhvatulin AI; Logunov DY; Naroditsky BS; Gintsburg AL
[Ad] Endereço:Gamaleya Institute of Epidemiology and Microbiology, Ministry of Health of Russian Federation, Gamaleya Street 18, Moscow 123098, Russia.
[Ti] Título:Chlamydial Type III Secretion System Needle Protein Induces Protective Immunity against Intravaginal Infection.
[So] Source:Biomed Res Int;2017:3865802, 2017.
[Is] ISSN:2314-6141
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:imposes serious health problems and causes infertility. Because of asymptomatic onset, it often escapes antibiotic treatment. Therefore, vaccines offer a better option for the prevention of unwanted inflammatory sequelae. The existence of serologically distinct serovars of suggests that a vaccine will need to provide protection against multiple serovars. spp. use a highly conserved type III secretion system (T3SS) composed of structural and effector proteins which is an essential virulence factor. In this study, we expressed the T3SS needle protein of TC_0037, an ortholog of CdsF, in a replication-defective adenoviral vector (AdTC_0037) and evaluated its protective efficacy in an intravaginal model. For better immune responses, we employed a heterologous prime-boost immunization protocol in which mice were intranasally primed with AdTC_0037 and subcutaneously boosted with recombinant TC_0037 and Toll-like receptor 4 agonist monophosphoryl lipid A mixed in a squalene nanoscale emulsion. We found that immunization with TC_0037 antigen induced specific humoral and T cell responses, decreased loads in the genital tract, and abrogated pathology of upper genital organs. Together, our results suggest that TC_0037, a highly conserved chlamydial T3SS protein, is a good candidate for inclusion in a vaccine.
[Mh] Termos MeSH primário: Proteínas de Bactérias
Vacinas Bacterianas
Infecções por Chlamydia
Chlamydia muridarum
Sistemas de Secreção Tipo III
[Mh] Termos MeSH secundário: Administração Intranasal
Animais
Proteínas de Bactérias/genética
Proteínas de Bactérias/imunologia
Vacinas Bacterianas/genética
Vacinas Bacterianas/imunologia
Infecções por Chlamydia/imunologia
Infecções por Chlamydia/microbiologia
Infecções por Chlamydia/prevenção & controle
Chlamydia muridarum/genética
Chlamydia muridarum/imunologia
Modelos Animais de Doenças
Feminino
Imunização
Camundongos
Camundongos Endogâmicos BALB C
Sistemas de Secreção Tipo III/genética
Sistemas de Secreção Tipo III/imunologia
Vacinas de DNA/genética
Vacinas de DNA/imunologia
Doenças Vaginais/imunologia
Doenças Vaginais/microbiologia
Doenças Vaginais/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bacterial Vaccines); 0 (Type III Secretion Systems); 0 (Vaccines, DNA)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1155/2017/3865802


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[PMID]:28449719
[Au] Autor:Bongard N; Lapuente D; Windmann S; Dittmer U; Tenbusch M; Bayer W
[Ad] Endereço:Institute for Virology, University Hospital Essen, University Duisburg-Essen, Virchowstr. 179, 45147, Essen, Germany.
[Ti] Título:Interference of retroviral envelope with vaccine-induced CD8 T cell responses is relieved by co-administration of cytokine-encoding vectors.
[So] Source:Retrovirology;14(1):28, 2017 Apr 27.
[Is] ISSN:1742-4690
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Retroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8 T cell responses towards another, simultaneously or subsequently delivered, immunogen. RESULTS: In the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL -specific CD8 T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid. In order to overcome this interference of retroviral envelope, we employed plasmids encoding the cytokines interleukin (IL) 1ß, IL2, IL12, IL15, IL21, IL28A or granulocyte-macrophage colony-stimulating factor (GM-CSF) as genetic adjuvants. Co-application of plasmids encoding IL2, IL12, IL21, IL28A and especially GM-CSF rescued the induction of GagL -specific CD8 T cells in mice vaccinated with FV Leader-Gag and Env. Mice that were immunized with plasmids encoding Leader-Gag and Env and the cytokines IL1ß, IL12, IL15, IL28A or GM-CSF, but not Leader-Gag and Env without any cytokine, showed significantly reduced viral loads upon a high-dose Friend virus challenge infection. CONCLUSIONS: Our data demonstrate the potency of cytokine-encoding vectors as adjuvants and immune modulators in composite vaccines for anti-retroviral immunization.
[Mh] Termos MeSH primário: Linfócitos T CD8-Positivos/imunologia
Citocinas/genética
Vírus da Leucemia Murina de Friend/imunologia
Vacinas de DNA/imunologia
Proteínas do Envelope Viral/imunologia
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos
Animais
Citocinas/imunologia
Feminino
Vírus da Leucemia Murina de Friend/genética
Produtos do Gene gag/genética
Produtos do Gene gag/imunologia
Vetores Genéticos
Imunização
Imunomodulação
Interleucina-15/genética
Interleucina-15/imunologia
Interleucina-2/genética
Interleucina-2/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Plasmídeos
Infecções por Retroviridae/imunologia
Vacinas de DNA/administração & dosagem
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/metabolismo
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Cytokines); 0 (Gene Products, gag); 0 (Interleukin-15); 0 (Interleukin-2); 0 (Vaccines, DNA); 0 (Viral Envelope Proteins); 0 (Viral Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12977-017-0352-7


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[PMID]:29267331
[Au] Autor:Koday MT; Leonard JA; Munson P; Forero A; Koday M; Bratt DL; Fuller JT; Murnane R; Qin S; Reinhart TA; Duus K; Messaoudi I; Hartman AL; Stefano-Cole K; Morrison J; Katze MG; Fuller DH
[Ad] Endereço:Department of Microbiology, University of Washington, Seattle, WA, United States of America.
[Ti] Título:Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates.
[So] Source:PLoS One;12(12):e0189780, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemics. We investigated immunogenicity and protective efficacy of a multi-antigen (MA) universal influenza DNA vaccine consisting of HA, M2, and NP antigens in cynomolgus macaques. Following challenge with a heterologous pandemic H1N1 strain, vaccinated animals exhibited significantly lower viral loads and more rapid viral clearance when compared to unvaccinated controls. The MA DNA vaccine induced robust serum and mucosal antibody responses but these high antibody titers were not broadly neutralizing. In contrast, the vaccine induced broadly-reactive NP specific T cell responses that cross-reacted with the challenge virus and inversely correlated with lower viral loads and inflammation. These results demonstrate that a MA DNA vaccine that induces strong cross-reactive T cell responses can, independent of neutralizing antibody, mediate significant cross-protection in a nonhuman primate model and further supports development as an effective approach to induce broad protection against circulating and emerging influenza strains.
[Mh] Termos MeSH primário: Reações Cruzadas
Vacinas contra Influenza/imunologia
Linfócitos T/imunologia
Vacinas de DNA/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/imunologia
Vírus da Influenza A Subtipo H1N1/imunologia
Vacinas contra Influenza/genética
Macaca fascicularis
Vacinas de DNA/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Influenza Vaccines); 0 (Vaccines, DNA)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180214
[Lr] Data última revisão:
180214
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189780


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[PMID]:29320562
[Au] Autor:Jarosz-Biej M; Kaminska N; Matuszczak S; Cichon T; Pamula-Pilat J; Czapla J; Smolarczyk R; Skwarzynska D; Kulik K; Szala S
[Ad] Endereço:Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, Gliwice, Poland.
[Ti] Título:M1-like macrophages change tumor blood vessels and microenvironment in murine melanoma.
[So] Source:PLoS One;13(1):e0191012, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tumor-associated macrophages (TAMs) play a significant role in at least two key processes underlying neoplastic progression: angiogenesis and immune surveillance. TAMs phenotypic changes play important role in tumor vessel abnormalization/ normalization. M2-like TAMs stimulate immunosuppression and formation of defective tumor blood vessels leading to tumor progression. In contrast M1-like TAMs trigger immune response and normalize irregular tumor vascular network which should sensitize cancer cells to chemo- and radiotherapy and lead to tumor growth regression. Here, we demonstrated that combination of endoglin-based DNA vaccine with interleukin 12 repolarizes TAMs from tumor growth-promoting M2-like phenotype to tumor growth-inhibiting M1-like phenotype. Combined therapy enhances tumor infiltration by CD4+, CD8+ lymphocytes and NK cells. Depletion of TAMs as well as CD8+ lymphocytes and NK cells, but not CD4+ lymphocytes, reduces the effect of combined therapy. Furthermore, combined therapy improves tumor vessel maturation, perfusion and reduces hypoxia. It caused that suboptimal doses of doxorubicin reduced the growth of tumors in mice treated with combined therapy. To summarize, combination of antiangiogenic drug and immunostimulatory agent repolarizes TAMs phenotype from M2-like (pro-tumor) into M1-like (anti-tumor) which affects the structure of tumor blood vessels, improves the effect of chemotherapy and leads to tumor growth regression.
[Mh] Termos MeSH primário: Interleucina-12/administração & dosagem
Macrófagos/fisiologia
Melanoma Experimental/irrigação sanguínea
Melanoma Experimental/imunologia
Neovascularização Patológica/patologia
Microambiente Tumoral/imunologia
[Mh] Termos MeSH secundário: Inibidores da Angiogênese/administração & dosagem
Animais
Antibióticos Antineoplásicos/farmacologia
Linfócitos T CD4-Positivos/efeitos dos fármacos
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/efeitos dos fármacos
Linfócitos T CD8-Positivos/imunologia
Proliferação Celular/efeitos dos fármacos
Doxorrubicina/farmacologia
Feminino
Células Matadoras Naturais/efeitos dos fármacos
Células Matadoras Naturais/imunologia
Macrófagos/efeitos dos fármacos
Melanoma Experimental/tratamento farmacológico
Melanoma Experimental/patologia
Camundongos
Camundongos Endogâmicos C57BL
Neovascularização Patológica/tratamento farmacológico
Neovascularização Patológica/imunologia
Células Tumorais Cultivadas
Vacinas de DNA/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Angiogenesis Inhibitors); 0 (Antibiotics, Antineoplastic); 0 (Vaccines, DNA); 187348-17-0 (Interleukin-12); 80168379AG (Doxorubicin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191012


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[PMID]:29193199
[Au] Autor:Liu C; Xie Y; Sun B; Geng F; Zhang F; Guo Q; Wu H; Yu B; Wu J; Yu X; Kong W; Zhang H
[Ad] Endereço:National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, China.
[Ti] Título:MUC1- and Survivin-based DNA Vaccine Combining Immunoadjuvants CpG and interleukin-2 in a Bicistronic Expression Plasmid Generates Specific Immune Responses and Antitumour Effects in a Murine Colorectal Carcinoma Model.
[So] Source:Scand J Immunol;87(2):63-72, 2018 Feb.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:DNA vaccination is a promising cancer treatment due to its safety, but poor immunogenicity limits its application. However, immunoadjuvants, heterogeneous prime-boost strategies and combination with conventional treatments can be used to improve the antitumour immune effects. A CpG motif and interleukin-2 (IL-2) cytokine are often used as adjuvants. In this study, a DNA vaccine containing a CpG motif was constructed to evaluate its adjuvant effect. The results show that the cytotoxicity of the DNA vaccine was increased fivefold, and survival lifetime was prolonged twofold by the CpG motif adjuvant. To simplify the industrial production process, a bicistronic plasmid was constructed to carry the fusion genes of survivin/MUC1 (MS) and IL-2 and with a CpG motif in its backbone. The results showed that the antitumour effect of the bicistronic vaccine was the same as that of the two vaccine co-injected regime. Furthermore, the vaccine could suppress metastatic tumour foci by 69.1% in colorectal carcinoma-bearing mice. Moreover, the vaccine induced survivin- and MUC1-specific immune responses in splenocytes and induced the immune promoting factor CCL-19 and GM-CSF upregulated, while metastatic-associated factor MMP-9 and immunosuppressing factor PD-L1 downregulated in tumour tissue. When combining the vaccine with the chemotherapy drug oxaliplatin, the survival was prolonged by about 2.5-fold. In conclusion, the DNA vaccine containing a CpG motif in bicistronic form showed good effects on colorectal cancer by inhibiting both tumour growth and metastasis, and combination with oxaliplatin could improve its antitumour effects.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/genética
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Vacinas Anticâncer/imunologia
Neoplasias Colorretais/imunologia
Proteínas Inibidoras de Apoptose/genética
Mucina-1/genética
Oligodesoxirribonucleotídeos/genética
Compostos Organoplatínicos/uso terapêutico
Proteínas Repressoras/genética
Vacinas de DNA/imunologia
[Mh] Termos MeSH secundário: Animais
Vacinas Anticâncer/genética
Processos de Crescimento Celular
Linhagem Celular Tumoral
Neoplasias Colorretais/terapia
Modelos Animais de Doenças
Feminino
Genes/genética
Seres Humanos
Imunidade
Interleucina-2/administração & dosagem
Interleucina-2/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Metástase Neoplásica
Plasmídeos
Vacinas de DNA/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Birc5 protein, mouse); 0 (CPG-oligonucleotide); 0 (Cancer Vaccines); 0 (Inhibitor of Apoptosis Proteins); 0 (Interleukin-2); 0 (Mucin-1); 0 (Oligodeoxyribonucleotides); 0 (Organoplatinum Compounds); 0 (Repressor Proteins); 0 (Vaccines, DNA); 0 (muc1 protein, mouse); 04ZR38536J (oxaliplatin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12633


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[PMID]:28470626
[Au] Autor:Sun L; Yuan Q; Xu T; Yao L; Feng J; Ma J; Wang L; Lv C; Wang D
[Ad] Endereço:Department of Nephrology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, People's Republic of China.
[Ti] Título:Novel adjuvant for immunization against tuberculosis: DNA vaccine expressing Mycobacterium tuberculosis antigen 85A and interleukin-15 fusion product elicits strong immune responses in mice.
[So] Source:Biotechnol Lett;39(8):1159-1166, 2017 Aug.
[Is] ISSN:1573-6776
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To investigate the potential of interleukin (IL)-15 as a novel adjuvant for Mycobacterium tuberculosis (Mtb) antigen 85A (Ag85A) vaccine. RESULTS: C57BL/6 mice were intramuscularly immunized three times with a plasmid expressing the Ag85A-IL-15 fusion protein (pcDNA3.1-Ag85A-IL-15), with the empty pcDNA3.1 vector and the pcDNA3.1-Ag85A as control. Mice vaccinated with pcDNA3.1-Ag85A-IL-15 generated more secretory IgA (sIgA) into their lung (209 ± 21 µg/ml) and acquired an enhanced serum IgG response to Ag85A. IgG2a/IgG1 ratios were upregulated, natural killer cell activity was augmented and Ag85A-specific splenic T cell proliferation was enhanced in these mice as well. Vaccination with pcDNA3.1-Ag85A-IL-15 promoted the polarization of CD4 T cells towards a Th1 type in the spleen, and significantly upregulated the serum level of interferon (IFN)-γ (458 ± 98 pg/ml), a typical Th1 cytokine. IFN-γ-expressing CD8 cells were also increased in the spleen after pcDNA3.1-Ag85A-IL-15 immunization. CONCLUSIONS: A superior immune type I response in mice vaccinated with plasmid Ag85A-IL-15 has been achieved.
[Mh] Termos MeSH primário: Aciltransferases/imunologia
Adjuvantes Imunológicos
Antígenos de Bactérias/imunologia
Interferon gama/imunologia
Proteínas Recombinantes de Fusão/imunologia
Vacinas contra a Tuberculose/imunologia
Vacinas de DNA/imunologia
[Mh] Termos MeSH secundário: Aciltransferases/química
Aciltransferases/genética
Adjuvantes Imunológicos/química
Adjuvantes Imunológicos/genética
Animais
Antígenos de Bactérias/química
Antígenos de Bactérias/genética
Líquido da Lavagem Broncoalveolar/citologia
Células Cultivadas
Clonagem Molecular
Células HEK293
Seres Humanos
Interferon gama/química
Interferon gama/genética
Camundongos
Camundongos Endogâmicos C57BL
Plasmídeos
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/genética
Baço/citologia
Tuberculose
Vacinas contra a Tuberculose/química
Vacinas contra a Tuberculose/genética
Vacinas de DNA/química
Vacinas de DNA/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antigens, Bacterial); 0 (Recombinant Fusion Proteins); 0 (Tuberculosis Vaccines); 0 (Vaccines, DNA); 82115-62-6 (Interferon-gamma); EC 2.3.- (Acyltransferases); EC 2.3.1.- (antigen 85A, Mycobacterium tuberculosis)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180202
[Lr] Data última revisão:
180202
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1007/s10529-017-2342-1


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[PMID]:28451790
[Au] Autor:Samuels S; Marijne Heeren A; Zijlmans HJMAA; Welters MJP; van den Berg JH; Philips D; Kvistborg P; Ehsan I; Scholl SME; Nuijen B; Schumacher TNM; van Beurden M; Jordanova ES; Haanen JBAG; van der Burg SH; Kenter GG
[Ad] Endereço:Department of Gynecology, Center for Gynecologic Oncology Amsterdam, P.O. Box 90203, 1006 BE, Amsterdam, The Netherlands.
[Ti] Título:HPV16 E7 DNA tattooing: safety, immunogenicity, and clinical response in patients with HPV-positive vulvar intraepithelial neoplasia.
[So] Source:Cancer Immunol Immunother;66(9):1163-1173, 2017 Sep.
[Is] ISSN:1432-0851
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Usual type vulvar intraepithelial neoplasia (uVIN) is caused by HPV, predominantly type 16. Several forms of HPV immunotherapy have been studied, however, clinical results could be improved. A novel intradermal administration route, termed DNA tattooing, is superior in animal models, and was tested for the first time in humans with a HPV16 E7 DNA vaccine (TTFC-E7SH). METHODS: The trial was designed to test safety, immunogenicity, and clinical response of TTFC-E7SH in twelve HPV16 uVIN patients. Patients received six vaccinations via DNA tattooing. The first six patients received 0.2 mg TTFC-E7SH and the next six 2 mg TTFC-E7SH. Vaccine-specific T-cell immunity was evaluated by IFNγ-ELISPOT and multiparametric flow cytometry. RESULTS: Only grade I-II adverse events were observed upon TTFC-E7SH vaccination. The ELISPOT analysis showed in 4/12 patients a response to the peptide pool containing shuffled E7 peptides. Multiparametric flow cytometry showed low CD4 and/or CD8 T-cell responses as measured by increased expression of PD-1 (4/12 in both), CTLA-4 (2/12 and 3/12), CD107a (5/12 and 4/12), or the production of IFNγ (2/12 and 1/12), IL-2 (3/12 and 4/12), TNFα (2/12 and 1/12), and MIP1ß (3/12 and 6/12). At 3 months follow-up, no clinical response was observed in any of the twelve vaccinated patients. CONCLUSION: DNA tattoo vaccination was shown to be safe. A low vaccine-induced immune response and no clinical response were observed in uVIN patients after TTFC-E7SH DNA tattoo vaccination. Therefore, a new phase I/II trial with an improved DNA vaccine format is currently in development for patients with uVIN.
[Mh] Termos MeSH primário: DNA/genética
Papillomavirus Humano 16/genética
Proteínas Oncogênicas Virais/imunologia
Vacinas de DNA/imunologia
Neoplasias Vulvares/genética
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Meia-Idade
Neoplasias Vulvares/terapia
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oncogene Proteins, Viral); 0 (Vaccines, DNA); 9007-49-2 (DNA)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180108
[Lr] Data última revisão:
180108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1007/s00262-017-2006-y


  9 / 8651 MEDLINE  
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[PMID]:29020058
[Au] Autor:McCurley NP; Domi A; Basu R; Saunders KO; LaBranche CC; Montefiori DC; Haynes BF; Robinson HL
[Ad] Endereço:GeoVax Inc., Smyrna, GA, United States of America.
[Ti] Título:HIV transmitted/founder vaccines elicit autologous tier 2 neutralizing antibodies for the CD4 binding site.
[So] Source:PLoS One;12(10):e0177863, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Here we report the construction, antigenicity and initial immunogenicity testing of DNA and modified vaccinia Ankara (MVA) vaccines expressing virus-like particles (VLPs) displaying sequential clade C Envelopes (Envs) that co-evolved with the elicitation of broadly neutralizing antibodies (bnAbs) to the CD4 binding site (CD4bs) in HIV-infected individual CH0505. The VLP-displayed Envs showed reactivity for conformational epitopes displayed on the receptor-binding form of Env. Two inoculations of the DNA-T/F vaccine, followed by 3 inoculations of the MVA-T/F vaccine and a final inoculation of the MVA-T/F plus a gp120-T/F protein vaccine elicited nAb to the T/F virus in 2 of 4 rhesus macaques (ID50 of ~175 and ~30). Neutralizing Ab plateaued at 100% neutralization and mapped to the CD4bs like the bnAbs elicited in CH0505. The nAb did not have breadth for other tier 2 viruses. Immunizations with T/F followed by directed-lineage vaccines, both with and without co-delivery of directed-lineage gp120 boosts, failed to elicit tier 2 neutralizing Ab for the CD4bs. Thus, pulsed exposures to DNA and MVA-expressed VLPs plus gp120 protein of a T/F Env can induce autologous tier 2 nAbs to the CD4bs.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Neutralizantes/imunologia
Antígenos CD4/metabolismo
Infecções por HIV/imunologia
Infecções por HIV/transmissão
[Mh] Termos MeSH secundário: Animais
Formação de Anticorpos/imunologia
Sítios de Ligação
Feminino
Células HEK293
Antígenos HIV/imunologia
Seres Humanos
Macaca mulatta
Vacinas de DNA/imunologia
Vírus Vaccinia/imunologia
Vírus Vaccinia/ultraestrutura
Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (HIV Antigens); 0 (Vaccines, DNA); 0 (env Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0177863


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[PMID]:28938099
[Au] Autor:Nickols B; Tretyakova I; Tibbens A; Klyushnenkova E; Pushko P
[Ad] Endereço:Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA.
[Ti] Título:Plasmid DNA launches live-attenuated Japanese encephalitis virus and elicits virus-neutralizing antibodies in BALB/c mice.
[So] Source:Virology;512:66-73, 2017 Dec.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We describe novel plasmid DNA that encodes the full-length Japanese encephalitis virus (JEV) genomic cDNA and launches live-attenuated JEV vaccine in vitro and in vivo. The synthetic cDNA based on the sequence of JEV SA14-14-2 live-attenuated virus was placed under transcriptional control of the cytomegalovirus major immediate-early promoter. The stability and yields of the plasmid in E. coli were optimized by inserting three synthetic introns that disrupted JEV cDNA in the structural and nonstructural genes. Transfection of Vero cells with the resulting plasmid resulted in the replication of JEV vaccine virus with intron sequences removed from viral RNA. Furthermore, a single-dose vaccination of BALB/c mice with 0.5 - 5µg of plasmid resulted in successful seroconversion and elicitation of JEV virus-neutralizing serum antibodies. The results demonstrate the possibility of using DNA vaccination to launch live-attenuated JEV vaccine and support further development of DNA-launched live-attenuated vaccine for prevention of JEV infections.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Anticorpos Antivirais/imunologia
DNA Complementar/imunologia
Vírus da Encefalite Japonesa (Espécie)/genética
Plasmídeos/genética
[Mh] Termos MeSH secundário: Animais
DNA Complementar/genética
Encefalite Japonesa/prevenção & controle
Camundongos
Camundongos Endogâmicos BALB C
Vacinas de DNA/imunologia
Vacinas Virais/imunologia
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (DNA, Complementary); 0 (Vaccines, DNA); 0 (Viral Vaccines)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE



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