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[PMID]:28453838
[Au] Autor:Lindesmith LC; Mallory ML; Jones TA; Richardson C; Goodwin RR; Baehner F; Mendelman PM; Bargatze RF; Baric RS
[Ad] Endereço:Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.
[Ti] Título:Impact of Pre-exposure History and Host Genetics on Antibody Avidity Following Norovirus Vaccination.
[So] Source:J Infect Dis;215(6):984-991, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no increase in titer following a second vaccine dose. Methods: Blockade Ab relative avidity was evaluated by measuring the slope of blockade Ab neutralization curves. Results: Blockade Ab avidity to the GI.1 vaccine component peaked at day 35 (7 days after dose 2). Avidities to heterotypic genogroup I VLPs were not sustained at day 35 after vaccination or GI.1 infection, as measured from archived sera. Only secretor-positive participants maintained high avidity blockade Ab to GI.1 at day 180. Avidity to the GII.4c vaccine component peaked at day 7, remained elevated through day 180, and was not secretor dependent. Avidity to an immunologically novel GII.4 strain VLP correlated with preexisting Ab titer to an ancestral strain Epitope A. Conclusions: Host genetics and pre-exposure history shape norovirus vaccine Ab responses, including blockade Ab avidity. Avidity of potentially neutralizing Ab may be an important metric for evaluating vaccine responses to highly penetrant viruses with cross-reactive serotypes.
[Mh] Termos MeSH primário: Afinidade de Anticorpos
Infecções por Caliciviridae/prevenção & controle
Vacinas de Partículas Semelhantes a Vírus/uso terapêutico
Vacinas Virais/uso terapêutico
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem
Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Anticorpos Neutralizantes/sangue
Anticorpos Antivirais/sangue
Infecções por Caliciviridae/genética
Reações Cruzadas
Método Duplo-Cego
Epitopos/imunologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Norovirus
Estados Unidos
Vacinação
Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
Vacinas Virais/administração & dosagem
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE; MULTICENTER STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Epitopes); 0 (Vaccines, Virus-Like Particle); 0 (Viral Vaccines)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix045


  2 / 619 MEDLINE  
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[PMID]:29338045
[Au] Autor:Kim AR; Lee DH; Lee SH; Rubino I; Choi HJ; Quan FS
[Ad] Endereço:Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, Korea.
[Ti] Título:Protection induced by virus-like particle vaccine containing tandem repeat gene of respiratory syncytial virus G protein.
[So] Source:PLoS One;13(1):e0191277, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract illness in infants, young children and the elderly. However, there is no licensed vaccine available against RSV infection. In this study, we generated virus-like particle (VLP) vaccine and investigated the vaccine efficacy in a mouse model. For VLP vaccines, tandem gene (1-780 bp) for V1 VLPs and tandem repeat gene (repeated 450-780 bp) for V5 VLPs were constructed in pFastBacTM vectors, respectively. Influenza matrix protein 1 (M1) was used as a core protein in the VLPs. Notably, upon challenge infection, significantly lower virus loads were measured in the lung of mice immunized with V1 or V5 VLPs compared to those of naïve mice and formalin-inactivated RSV immunized control mice. In particular, V5 VLPs immunization showed significantly lower virus titers than V1 VLPs immunization. Furthermore, V5 VLPs immunization elicited increased memory B cells responses in the spleen. These results indicated that V5 VLP vaccine containing tandem repeat gene protein provided better protection than V1 VLPs with significantly decreased inflammation in the lungs. Thus, V5 VLPs could be a potential vaccine candidate against RSV.
[Mh] Termos MeSH primário: Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/farmacologia
Vírus Sincicial Respiratório Humano/genética
Vírus Sincicial Respiratório Humano/imunologia
Vacinas de Partículas Semelhantes a Vírus/farmacologia
Proteínas do Envelope Viral/genética
Proteínas do Envelope Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/sangue
Modelos Animais de Doenças
Feminino
Genes Virais
Seres Humanos
Pulmão/imunologia
Pulmão/patologia
Pulmão/virologia
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Vírus Respiratório Sincicial/imunologia
Infecções por Vírus Respiratório Sincicial/virologia
Vacinas contra Vírus Sincicial Respiratório/genética
Sequências de Repetição em Tandem
Vacinas de Partículas Semelhantes a Vírus/genética
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Respiratory Syncytial Virus Vaccines); 0 (Vaccines, Virus-Like Particle); 0 (Viral Envelope Proteins); 0 (attachment protein G)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191277


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[PMID]:29324805
[Au] Autor:Lee YT; Ko EJ; Lee Y; Kim KH; Kim MC; Lee YN; Kang SM
[Ad] Endereço:Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, United States of America.
[Ti] Título:Intranasal vaccination with M2e5x virus-like particles induces humoral and cellular immune responses conferring cross-protection against heterosubtypic influenza viruses.
[So] Source:PLoS One;13(1):e0190868, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Current influenza vaccines do not provide broad cross-protection. Here, we report that intranasal vaccination with virus-like particles containing the highly conserved multiple ectodomains of matrix protein 2 (M2e5x VLP) of influenza virus induces broad cross-protection by M2-specific humoral and cellular immune responses. M2e5x VLP intranasal vaccination prevented severe weight loss, attenuated inflammatory cytokines and cellular infiltrates, and lowered viral loads, and induced germinal center phenotypic B and plasma cells. In addition, depletion studies demonstrate the protective roles of CD4 and CD8 T cells induced by M2e5x VLP intranasal vaccination. Thus, this study provides evidence that mucosal delivery of M2e5x VLP vaccine provides cross-protection by inducing humoral and cellular immune responses.
[Mh] Termos MeSH primário: Proteção Cruzada
Vírus da Influenza A Subtipo H3N2/imunologia
Vírus da Influenza A Subtipo H5N1/imunologia
Vacinas contra Influenza/administração & dosagem
Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
Proteínas da Matriz Viral/imunologia
[Mh] Termos MeSH secundário: Administração Intranasal
Animais
Anticorpos Antivirais/análise
Anticorpos Antivirais/sangue
Linfócitos B/imunologia
Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Embrião de Galinha
Feminino
Pulmão/imunologia
Pulmão/virologia
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/imunologia
Infecções por Orthomyxoviridae/prevenção & controle
Infecções por Orthomyxoviridae/virologia
Células Sf9
Spodoptera
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Influenza Vaccines); 0 (Vaccines, Virus-Like Particle); 0 (Viral Matrix Proteins)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190868


  4 / 619 MEDLINE  
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[PMID]:28458036
[Au] Autor:Meador LR; Kessans SA; Kilbourne J; Kibler KV; Pantaleo G; Roderiguez ME; Blattman JN; Jacobs BL; Mor TS
[Ad] Endereço:Ira A. Fulton School of Engineering, Arizona State University, Tempe, AZ, USA; Center for Infectious Diseases and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ, USA.
[Ti] Título:A heterologous prime-boosting strategy with replicating Vaccinia virus vectors and plant-produced HIV-1 Gag/dgp41 virus-like particles.
[So] Source:Virology;507:242-256, 2017 07.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Showing modest efficacy, the RV144 HIV-1 vaccine clinical trial utilized a non-replicating canarypox viral vector and a soluble gp120 protein boost. Here we built upon the RV144 strategy by developing a novel combination of a replicating, but highly-attenuated Vaccinia virus vector, NYVAC-KC, and plant-produced HIV-1 virus-like particles (VLPs). Both components contained the full-length Gag and a membrane anchored truncated gp41 presenting the membrane proximal external region with its conserved broadly neutralizing epitopes in the pre-fusion conformation. We tested different prime/boost combinations of these components in mice and showed that the group primed with NYVAC-KC and boosted with both the viral vectors and plant-produced VLPs have the most robust Gag-specific CD8 T cell responses, at 12.7% of CD8 T cells expressing IFN-γ in response to stimulation with five Gag epitopes. The same immunization group elicited the best systemic and mucosal antibody responses to Gag and dgp41 with a bias towards IgG1.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/administração & dosagem
Proteína gp41 do Envelope de HIV/imunologia
Infecções por HIV/imunologia
HIV-1/imunologia
Imunização/métodos
Tabaco/metabolismo
Vírus Vaccinia/fisiologia
Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/imunologia
Animais
Anticorpos Neutralizantes/imunologia
Formação de Anticorpos
Feminino
Vetores Genéticos/genética
Vetores Genéticos/fisiologia
Anticorpos Anti-HIV/imunologia
Proteína gp41 do Envelope de HIV/administração & dosagem
Proteína gp41 do Envelope de HIV/genética
Infecções por HIV/prevenção & controle
Infecções por HIV/virologia
HIV-1/genética
Seres Humanos
Imunização Secundária
Camundongos
Camundongos Endogâmicos C57BL
Tabaco/genética
Tabaco/virologia
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
Vírus Vaccinia/genética
Replicação Viral
Produtos do Gene gag do Vírus da Imunodeficiência Humana/administração & dosagem
Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp41); 0 (Vaccines, Virus-Like Particle); 0 (gag Gene Products, Human Immunodeficiency Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  5 / 619 MEDLINE  
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[PMID]:28938005
[Au] Autor:Holanda RA; Muñoz JE; Dias LS; Silva LBR; Santos JRA; Pagliari S; Vieira ÉLM; Paixão TA; Taborda CP; Santos DA; Bruña-Romero O
[Ad] Endereço:Departamento de Microbiologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
[Ti] Título:Recombinant vaccines of a CD4+ T-cell epitope promote efficient control of Paracoccidioides brasiliensis burden by restraining primary organ infection.
[So] Source:PLoS Negl Trop Dis;11(9):e0005927, 2017 Sep.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Paracoccidioidomycosis (PCM) is an infectious disease endemic to South America, caused by the thermally dimorphic fungi Paracoccidioides. Currently, there is no effective human vaccine that can be used in prophylactic or therapeutic regimes. We tested the hypothesis that the immunogenicity of the immunodominant CD4+ T-cell epitope (P10) of Paracoccidioides brasiliensis gp43 antigen might be significantly enhanced by using a hepatitis B virus-derived particle (VLP) as an antigen carrier. This chimera was administered to mice as a (His)6-purified protein (rPbT) or a replication-deficient human type 5 adenoviral vector (rAdPbT) in an immunoprophylaxis assay. The highly virulent Pb18 yeast strain was used to challenge our vaccine candidates. Fungal challenge evoked robust P10-specific memory CD4+ T cells secreting protective Th-1 cytokines in most groups of immunized mice. Furthermore, the highest level of fungal burden control was achieved when rAdPbT was inoculated in a homologous prime-boost regimen, with 10-fold less CFU recovering than in non-vaccinated mice. Systemic Pb18 spreading was only prevented when rAdPbT was previously inoculated. In summary, we present here VLP/P10 formulations as vaccine candidates against PCM, some of which have demonstrated for the first time their ability to prevent progression of this pernicious fungal disease, which represents a significant social burden in developing countries.
[Mh] Termos MeSH primário: Antígenos de Fungos/imunologia
Linfócitos T CD4-Positivos/imunologia
Epitopos de Linfócito T/imunologia
Proteínas Fúngicas/imunologia
Vacinas Fúngicas/administração & dosagem
Glicoproteínas/imunologia
Paracoccidioides/crescimento & desenvolvimento
Paracoccidioides/imunologia
Paracoccidioidomicose/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Citocinas/imunologia
Citocinas/secreção
Epitopos de Linfócito T/genética
Vacinas Fúngicas/imunologia
Vírus da Hepatite B/genética
Imunização
Epitopos Imunodominantes/imunologia
Imunogenicidade da Vacina
Memória Imunológica
Fígado/microbiologia
Pulmão/microbiologia
Camundongos Endogâmicos BALB C
Paracoccidioidomicose/imunologia
Paracoccidioidomicose/microbiologia
Baço/microbiologia
Células Th1/imunologia
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (43 kDa protein, Paracoccidioides); 0 (Antigens, Fungal); 0 (Cytokines); 0 (Epitopes, T-Lymphocyte); 0 (Fungal Proteins); 0 (Fungal Vaccines); 0 (Glycoproteins); 0 (Immunodominant Epitopes); 0 (Vaccines, Synthetic); 0 (Vaccines, Virus-Like Particle)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171025
[Lr] Data última revisão:
171025
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005927


  6 / 619 MEDLINE  
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[PMID]:28846899
[Au] Autor:Hwang HS; Lee YT; Kim KH; Ko EJ; Lee Y; Kwon YM; Kang SM
[Ad] Endereço:Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA; Department of Microbiology, Chonnam National University Medical School, Gwangju, Republic of Korea.
[Ti] Título:Virus-like particle vaccine primes immune responses preventing inactivated-virus vaccine-enhanced disease against respiratory syncytial virus.
[So] Source:Virology;511:142-151, 2017 Nov.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Formalin inactivated respiratory syncytial virus (FI-RSV) vaccination caused vaccine-enhanced respiratory disease (ERD) upon exposure to RSV in children. Virus-like particles presenting RSV F fusion protein (F VLP) are known to increase T helper type-1 (Th1) immune responses and avoid ERD in animal models. We hypothesized that F VLP would prime immune responses preventing ERD upon subsequent exposure to ERD-prone FI-RSV. Here, we demonstrated that heterologous F VLP priming and FI-RSV boosting of mice prevented FI-RSV vaccine-enhanced lung inflammation and eosinophilia upon RSV challenge. F VLP priming redirected pulmonary T cells toward effector CD8 T cells producing Th1 cytokines and significantly suppressed pulmonary Th2 cytokines. This study suggests that RSV F VLP priming would modulate and shift immune responses to subsequent exposure to ERD-prone FI-RSV vaccine and RSV infection, suppressing Th2 immune-mediated pulmonary histopathology and eosinophilia.
[Mh] Termos MeSH primário: Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle
Infecções por Vírus Respiratório Sincicial/prevenção & controle
Vacinas contra Vírus Sincicial Respiratório/efeitos adversos
Vacinas contra Vírus Sincicial Respiratório/imunologia
Vírus Sinciciais Respiratórios/imunologia
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Mh] Termos MeSH secundário: Animais
Linfócitos T CD8-Positivos/imunologia
Citocinas/secreção
Camundongos
Células Th1/imunologia
Vacinas de Produtos Inativados/efeitos adversos
Vacinas de Produtos Inativados/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Respiratory Syncytial Virus Vaccines); 0 (Vaccines, Inactivated); 0 (Vaccines, Virus-Like Particle)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170829
[St] Status:MEDLINE


  7 / 619 MEDLINE  
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[PMID]:28794019
[Au] Autor:Garg H; Sedano M; Plata G; Punke EB; Joshi A
[Ad] Endereço:Center of Emphasis in Infectious Diseases, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, Texas, USA himanshu.garg@ttuhsc.edu anjali.joshi@ttuhsc.edu.
[Ti] Título:Development of Virus-Like-Particle Vaccine and Reporter Assay for Zika Virus.
[So] Source:J Virol;91(20), 2017 Oct 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recent worldwide outbreaks of Zika virus (ZIKV) infection and the lack of an approved vaccine raise serious concerns regarding preparedness to combat this emerging virus. We used a virus-like particle (VLP)-based approach to develop a vaccine and a microneutralization assay for ZIKV. A synthetic capsid-premembrane-envelope (C-prM-E) gene construct of ZIKV was used to generate reporter virus particles (RVPs) that package a green fluorescent protein (GFP) reporter-expressing West Nile virus (WNV) replicon. The assay was adapted to a 96-well format, similar to the plaque reduction neutralization test (PRNT), and showed high reproducibility with specific detection of ZIKV neutralizing antibodies. Furthermore, C-prM-E and prM-E VLPs were tested as vaccine candidates in mice and compared to DNA vaccination. While the ZIKV prM-E construct alone was sufficient for generating VLPs, efficient VLP production from the C-prM-E construct could be achieved in the presence of the WNV NS2B-3 protease, which cleaves C from prM, allowing virus release. Immunization studies in mice showed that VLPs generated higher neutralizing antibody titers than those with the DNA vaccines, with C-prM-E VLPs giving slightly higher titers than those with prM-E VLPs. The superiority of C-prM-E VLPs suggests that inclusion of capsid may have benefits for ZIKV and other flaviviral VLP vaccines. To facilitate the VLP platform, we generated a stable cell line expressing high levels of ZIKV prM-E proteins that constitutively produce VLPs as well as a cell line expressing ZIKV C-prM-E proteins for RVP production. While several vaccine platforms have been proposed for ZIKV, this study describes a safe, effective, and economical VLP-based vaccine against ZIKV. To address the growing Zika virus epidemic, we undertook this study with two objectives: first, to develop a safe, effective, and economical vaccine for ZIKV, and second, to develop a rapid and versatile assay to detect the anti-ZIKV immune response. We generated a cell line stably expressing ZIKV prM-E that produces large amounts of VLPs in the supernatant and a ZIKV C-prM-E cell line that produces reporter virus particles upon transfection with a GFP replicon plasmid. The prM-E VLPs induced a strong neutralizing antibody response in mice that was better when the capsid was included. VLP-based vaccines showed significantly better neutralizing antibody responses than those with their DNA counterparts. The RVP-based microneutralization assay worked similarly to the PRNT assay, with a rapid GFP readout in a 96-well format. Our VLP-based platform provides a source for a ZIKV vaccine and diagnosis that can rapidly be adapted to current outbreaks.
[Mh] Termos MeSH primário: Anticorpos Neutralizantes/imunologia
Anticorpos Antivirais/imunologia
Testes de Neutralização
Vacinas de Partículas Semelhantes a Vírus/imunologia
Vacinas Virais/imunologia
Infecção pelo Zika virus/prevenção & controle
Zika virus/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/biossíntese
Anticorpos Antivirais/biossíntese
Proteínas de Fluorescência Verde/genética
Camundongos
Reprodutibilidade dos Testes
Vacinas de DNA/administração & dosagem
Vacinas de DNA/imunologia
Vacinas de Partículas Semelhantes a Vírus/administração & dosagem
Vacinas de Partículas Semelhantes a Vírus/efeitos adversos
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas Virais/administração & dosagem
Vacinas Virais/efeitos adversos
Vacinas Virais/economia
Vírus do Nilo Ocidental/genética
Zika virus/isolamento & purificação
Infecção pelo Zika virus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Neutralizing); 0 (Antibodies, Viral); 0 (Vaccines, DNA); 0 (Vaccines, Virus-Like Particle); 0 (Viral Vaccines); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170811
[St] Status:MEDLINE


  8 / 619 MEDLINE  
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[PMID]:28787006
[Au] Autor:Chen WA; Zhang J; Hall KM; Martin CB; Kisselev S; Dasen EJ; Vahanian NN; Link CJ; Martin BK
[Ad] Endereço:NewLink Genetics Corp., Ames, Iowa, United States of America.
[Ti] Título:Addition of αGal HyperAcute™ technology to recombinant avian influenza vaccines induces strong low-dose antibody responses.
[So] Source:PLoS One;12(8):e0182683, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Highly pathogenic avian influenza represents a severe public health threat. Over the last decade, the demand for highly efficacious vaccines against avian influenza viruses has grown, especially after the 2013 H7N9 outbreak in China that resulted in over 600 human cases with over 200 deaths. Currently, there are several H5N1 and H7N9 influenza vaccines in clinical trials, all of which employ traditional oil-in-water adjuvants due to the poor immunogenicity of avian influenza virus antigens. In this study, we developed potent recombinant avian influenza vaccine candidates using HyperAcute™ Technology, which takes advantage of naturally-acquired anti-αGal immunity in humans. We successfully generated αGal-positive recombinant protein and virus-like particle vaccine candidates of H5N1 and H7N9 influenza strains using either biological or our novel CarboLink chemical αGal modification techniques. Strikingly, two doses of 100 ng αGal-modified vaccine, with no traditional adjuvant, was able to induce a much stronger humoral response in αGT BALB/c knockout mice (the only experimental system readily available for testing αGal in vivo) than unmodified vaccines even at 10-fold higher dose (1000 ng/dose). Our data strongly suggest that αGal modification significantly enhances the humoral immunogenicity of the recombinant influenza vaccine candidates. Use of αGal HyperAcute™ technology allows significant dose-sparing while retaining desired immunogenicity. Our success in the development of highly potent H5N1 and H7N9 vaccine candidates demonstrated the potential of αGal HyperAcute™ technology for the development of vaccines against other infectious diseases.
[Mh] Termos MeSH primário: Anticorpos Antivirais/imunologia
Vírus da Influenza A Subtipo H5N1/imunologia
Vírus da Influenza A Subtipo H7N9/imunologia
Vacinas contra Influenza/genética
Vacinas contra Influenza/imunologia
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Epitopos/imunologia
Feminino
Galactosiltransferases/deficiência
Galactosiltransferases/genética
Técnicas de Inativação de Genes
Imunidade Humoral/imunologia
Vacinas contra Influenza/química
Camundongos
Camundongos Endogâmicos BALB C
Vacinas Sintéticas/química
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Epitopes); 0 (Influenza Vaccines); 0 (Vaccines, Synthetic); 0 (Vaccines, Virus-Like Particle); EC 2.4.1.- (Galactosyltransferases); EC 2.4.1.133 (alpha 1,3 galactosyltransferase, mouse)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170809
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0182683


  9 / 619 MEDLINE  
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[PMID]:28732070
[Au] Autor:Zhao D; Sun B; Sun S; Fu B; Liu C; Liu D; Chu Y; Ma Y; Bai L; Wu Y; Zhou Y; Su W; Hou A; Cai L; Xu F; Kong W; Jiang C
[Ad] Endereço:National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, China.
[Ti] Título:Characterization of human enterovirus71 virus-like particles used for vaccine antigens.
[So] Source:PLoS One;12(7):e0181182, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Human enterovirus 71 (EV71) is a major causative pathogen of hand, foot and mouth disease (HFMD) and has caused outbreaks with significant mortality among young children in the Asia-Pacific region in recent years. Towards developing a vaccine for this disease, we have expressed and purified EV71 virus-like particles (VLPs), which resemble the authentic virus in appearance, capsid structure and protein sequence, from insect cells (Sf9) using a multistep chromatography process. We demonstrated intracellular localization of the VLPs in host cells by in situ immunogold detection, electron microscopy and immunofluorescence. Characteristics of these EV71 VLPs were studied using a variety of immunological and physicochemical techniques, which aimed to reveal that the purified EV71 VLPs have good morphology and structure consistent with natural EV71 empty capsids. Results of the amino acid analysis, SDS-PAGE, Western blotting and high-performance liquid chromatography confirmed the high purity of the EV71 VLPs. However the sedimentation coefficient of the VLPs showed that they were smaller than that of secreted EV71 VLPs purified by discontinuous cesium chloride density gradients, they were similar to the empty capsids of natural EV71 virions reported previously. Combined with the previous study that EV71 VLPs purified by a multistep chromatography process were able to elicit strong humoral immune responses in mice, our results further supported the conclusion that our EV71 VLPs had well-preserved molecular and structural characteristics. The EV71 VLPs produced from the baculovirus expression system and purified by a multistep chromatography process displayed key structural and immunological features, which would contribute to their efficacy as a HFMD vaccine.
[Mh] Termos MeSH primário: Enterovirus Humano A/imunologia
Vacinas de Partículas Semelhantes a Vírus/química
Vacinas de Partículas Semelhantes a Vírus/imunologia
Vacinas Virais/química
Vacinas Virais/imunologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Western Blotting
Cromatografia Líquida de Alta Pressão
Difusão Dinâmica da Luz
Eletroforese em Gel de Poliacrilamida
Enterovirus Humano A/genética
Imuno-Histoquímica
Espectrometria de Massas
Microscopia de Força Atômica
Microscopia Confocal
Microscopia Eletrônica de Transmissão
Células Sf9
Vacinas de Partículas Semelhantes a Vírus/genética
Vacinas de Partículas Semelhantes a Vírus/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vaccines, Virus-Like Particle); 0 (Viral Vaccines)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181182


  10 / 619 MEDLINE  
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[PMID]:28667757
[Au] Autor:Cervera L; González-Domínguez I; Segura MM; Gòdia F
[Ad] Endereço:Grup d'Enginyeria Cellular i Bioprocés, Escola d'Enginyeria, Universitat Autònoma de Barcelona, Campus de Bellaterra, Cerdanyola del Vallès, 08193, Barcelona, Spain.
[Ti] Título:Intracellular characterization of Gag VLP production by transient transfection of HEK 293 cells.
[So] Source:Biotechnol Bioeng;114(11):2507-2517, 2017 Nov.
[Is] ISSN:1097-0290
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Transient transfection is a fast, flexible, and cost-effective approach to produce biological products. Despite the continued interest in transient transfection, little is known regarding the transfection process at the intracellular level, particularly for complex products, such as virus-like particles (VLPs). The kinetics of PEI-mediated transfection following an established in-house protocol is reported in this work with the aim of characterizing and understanding the complete process leading to VLP generation and identifying important events driving process improvement. For this purpose, DNA/PEI polyplexes' internalization in cells was tracked using Cy3 DNA staining. The production of a fluorescently labeled Gag polyprotein (a Gag-GFP fusion construct that forms fluorescent Gag-VLPs) was monitored by flow cytometry and confocal microscopy, and the VLP concentration in supernatants was measured by fluorometry. DNA/PEI polyplexes interact with the cell membrane immediately after polyplex addition to the cell culture. A linear increase in the number of cells expressing the protein is observed during the first 60 min of contact between the cells and polyplexes. No additional improvement in the number of cells expressing the protein (up to 60%) or VLP production (up to 1 × 10 VLPs/mL) is observed with additional contact time between the cells and polyplexes. Polyplexes can be detected in the cytoplasm of transfected cells as early as 1.5 h post-transfection (hpt) and reach the nucleus approximately 4 hpt. GFP fluorescence is observed homogeneously in the cytoplasm of transfected cells 24 hpt, but generalized VLP budding is not observed by microscopy until 48 hpt. Although all cells have internalized a polyplex soon after transfection, only a fraction of cells (60%) express the fluorescent Gag protein. VLP production kinetics was also studied. Fluorescence in the supernatant (enveloped VLPs) is 40% less than total fluorescence, supernatant plus pellet (total Gag-GFP), indicating that there is a fraction of Gag that remains inside the cells. The maximum VLP concentration in the cell culture supernatant with cell viability >89% was observed at 72 hpt, which was determined to be the optimal harvest time. Biotechnol. Bioeng. 2017;114: 2507-2517. © 2017 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Produtos do Gene gag/genética
Engenharia de Proteínas/métodos
Proteínas Recombinantes/biossíntese
Transfecção/métodos
Vacinas de Partículas Semelhantes a Vírus/biossíntese
[Mh] Termos MeSH secundário: Células HEK293
Seres Humanos
Proteínas Recombinantes/genética
Vacinas de Partículas Semelhantes a Vírus/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Gene Products, gag); 0 (Recombinant Proteins); 0 (Vaccines, Virus-Like Particle)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170702
[St] Status:MEDLINE
[do] DOI:10.1002/bit.26367



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