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[PMID]:29187586
[Au] Autor:Banerjee A; Bhattacharya P; Dagur PK; Karmakar S; Ismail N; Joshi AB; Akue AD; KuKuruga M; McCoy JP; Dey R; Nakhasi HL
[Ad] Endereço:Division of Emerging and Transfusion Transmitted Diseases, Office of Blood Research and Review, Center for Biologics Evaluation and Research, Food and Drug Administration, Silver Spring, MD 20993.
[Ti] Título:Live Attenuated Centrin Gene-Deleted Parasites Induce IL-23-Dependent IL-17-Protective Immune Response against Visceral Leishmaniasis in a Murine Model.
[So] Source:J Immunol;200(1):163-176, 2018 01 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:No vaccine exists against visceral leishmaniasis. To develop effective vaccines, we have previously reported protective role of live attenuated centrin gene-deleted ( ) parasites through induction of Th1 type immune response in mice, hamsters, and dogs. In this study, we specifically explored the role of Th17 cells in -induced host protection in mice. Our results showed that compared with wild-type infection, parasites induce significantly higher expression of Th17 differentiation cytokines in splenic dendritic cells. There was also induction of IL-17 and its promoting cytokines in total splenocytes and in both CD4 and CD8 T cells following immunization with Upon challenge with wild-type parasites, IL-17 and its differentiating cytokines were significantly higher in -immunized mice compared with nonimmunized mice that resulted in parasite control. Alongside IL-17 induction, we observed induction of IFN-γ-producing Th1 cells as reported earlier. However, Th17 cells are generated before Th1 cells. Neutralization of either IL-17 or IFN-γ abrogated -induced host protection further confirming the essential role of Th17 along with Th1 cytokines in host protection. Treatment with recombinant IL-23, which is required for stabilization and maintenance of IL-17, heightened Th17, and Tc17 responses in immunized mice splenocytes. In contrast, Th17 response was absent in immunized IL-23R mice that failed to induce protection upon virulent challenge suggesting that IL-23 plays an essential role in IL-17-mediated protection by parasites. This study unveiled the role of IL-23-dependent IL-17 induction in parasite-induced immunity and subsequent protection against visceral leishmaniasis.
[Mh] Termos MeSH primário: Interleucina-17/metabolismo
Interleucina-23/metabolismo
Leishmania donovani/imunologia
Vacinas contra Leishmaniose/imunologia
Leishmaniose Visceral/imunologia
Células Th1/imunologia
Células Th17/imunologia
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Feminino
Seres Humanos
Leishmania donovani/genética
Vacinas contra Leishmaniose/genética
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Proteínas de Protozoários/genética
Receptores de Interleucina/genética
Células Th1/parasitologia
Células Th17/parasitologia
Vacinas Atenuadas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, P.H.S.
[Nm] Nome de substância:
0 (Interleukin-17); 0 (Interleukin-23); 0 (Leishmaniasis Vaccines); 0 (Protozoan Proteins); 0 (Receptors, Interleukin); 0 (Vaccines, Attenuated); 0 (interleukin-23 receptor, mouse)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180131
[Lr] Data última revisão:
180131
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171201
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700674


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[PMID]:29176865
[Au] Autor:Cecílio P; Pérez-Cabezas B; Fernández L; Moreno J; Carrillo E; Requena JM; Fichera E; Reed SG; Coler RN; Kamhawi S; Oliveira F; Valenzuela JG; Gradoni L; Glueck R; Gupta G; Cordeiro-da-Silva A
[Ad] Endereço:Parasite Disease group, Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
[Ti] Título:Pre-clinical antigenicity studies of an innovative multivalent vaccine for human visceral leishmaniasis.
[So] Source:PLoS Negl Trop Dis;11(11):e0005951, 2017 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative vaccine formulation represents a promising anti-Leishmania vaccine whose efficacy deserves to be tested in the context of the "natural infection".
[Mh] Termos MeSH primário: Anticorpos Antiprotozoários/sangue
Antígenos de Protozoários/imunologia
Imunogenicidade da Vacina
Vacinas contra Leishmaniose/imunologia
Leishmaniose Visceral/prevenção & controle
Saliva/imunologia
[Mh] Termos MeSH secundário: Adjuvantes Imunológicos/administração & dosagem
Animais
Seres Humanos
Imunidade Celular
Imunidade Humoral
Leishmania donovani
Leishmaniose Visceral/imunologia
Ativação Linfocitária
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Psychodidae/imunologia
Psychodidae/parasitologia
Proteínas Recombinantes/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antibodies, Protozoan); 0 (Antigens, Protozoan); 0 (Leishmaniasis Vaccines); 0 (Recombinant Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005951


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[PMID]:28988041
[Au] Autor:Dias DS; Ribeiro PAF; Martins VT; Lage DP; Portela ÁSB; Costa LE; Salles BCS; Lima MP; Ramos FF; Santos TTO; Caligiorne RB; Chávez-Fumagalli MA; Silveira JAG; Magalhães-Soares DF; Gonçalves DU; Oliveira JS; Roatt BM; Duarte MC; Menezes-Souza D; Silva ES; Galdino AS; Machado-de-Ávila RA; Teixeira AL; Coelho EAF
[Ad] Endereço:Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
[Ti] Título:Recombinant small glutamine-rich tetratricopeptide repeat-containing protein of Leishmania infantum: Potential vaccine and diagnostic application against visceral leishmaniasis.
[So] Source:Mol Immunol;91:272-281, 2017 11.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Different Leishmania proteins have been evaluated in order to find a potential vaccine candidate or diagnostic marker capable of providing long lasting protection against infection or helping to identify infected mammalian hosts, respectively. However, just few molecules have fulfilled all the requirements to be evaluated. In the current study, we evaluated the prophylactic and diagnostic value against visceral leishmaniasis (VL) of a small glutamine-rich tetratricopeptide repeat-containing (SGT) protein from Leishmania infantum species. In a first step, the immune response elicited by the immunization using the recombinant protein (rSGT) plus saponin was evaluated in BALB/c mice. Immunized animals had a low parasitism in all evaluated organs. They developed a specific Th1 immune response, which was based on protein-specific production of IFN-γ, IL-12 and GM-CSF, and a humoral response dominated by antibodies of the IgG2a isotype. Both CD4 and CD8 T cells contributed to the IFN-γ production, showing that both T cell subtypes contribute to the resistance against infection. Regarding its value as a diagnostic marker, rSGT showed maximum sensitivity and specificity to serologically identify L. infantum-infected dog and human sera. No cross-reactivity with sera from humans or dogs that had other diseases was found. Although further studies are necessary to validate these findings, data showed here suggest immunogenicity of rSGT and its protective effect against murine VL, as well as its potential for the serodiagnosis of human and canine VL.
[Mh] Termos MeSH primário: Leishmania infantum/imunologia
Vacinas contra Leishmaniose/imunologia
Leishmaniose Visceral/diagnóstico
Leishmaniose Visceral/prevenção & controle
Proteínas de Protozoários/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/imunologia
Linfócitos T CD8-Positivos/imunologia
Linfócitos T CD8-Positivos/patologia
Reações Cruzadas
Citocinas/imunologia
Cães
Feminino
Seres Humanos
Imunoglobulina G/imunologia
Leishmania infantum/genética
Vacinas contra Leishmaniose/genética
Leishmaniose Visceral/genética
Leishmaniose Visceral/imunologia
Camundongos Endogâmicos BALB C
Proteínas de Protozoários/genética
Proteínas de Protozoários/farmacologia
Proteínas Recombinantes/genética
Proteínas Recombinantes/imunologia
Proteínas Recombinantes/farmacologia
Células Th1/imunologia
Células Th1/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Cytokines); 0 (Immunoglobulin G); 0 (Leishmaniasis Vaccines); 0 (Protozoan Proteins); 0 (Recombinant Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171009
[St] Status:MEDLINE


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[PMID]:28968470
[Au] Autor:Sanya RE; Tumwesige E; Elliott AM; Seeley J
[Ad] Endereço:Immunomodulation and Vaccines Programme, Medical Research Council/ Uganda Virus Research Institute (MRC/ UVRI) Uganda Research Unit, Uganda Virus Research Institute, Entebbe, Uganda.
[Ti] Título:Perceptions about interventions to control schistosomiasis among the Lake Victoria island communities of Koome, Uganda.
[So] Source:PLoS Negl Trop Dis;11(10):e0005982, 2017 Oct.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Praziquantel-based mass treatment is the main approach to controlling schistosomiasis mansoni in endemic areas. Interventions such as provision and use of safe water, minimising contact with infested water, disposal of stool in latrines and snail control provide key avenues to break the transmission cycle and can sustain the benefits of mass treatment in the long term. Efforts are also being made to develop a schistosomiasis vaccine which, if effective, might reduce the incidence of re-infection after treatment. However, any interventions deployed need to be acceptable to, and sustainable by, the target communities. METHODS: In this qualitative study, we investigated the perceptions of six Lake Victoria island communities of Koome, Uganda, about interventions to control Schistosoma mansoni infection and their willingness to participate in Schistosoma vaccine trials. Thirty-two in-depth interviews, 12 key informant interviews and 10 focus group discussions were conducted. Data were analysed using a thematic content approach. FINDINGS: Intestinal schistosomiasis was not regarded as a serious health problem because a mass treatment programme is in place. However, the communities lack safe water sources and latrines. Mass treatment with praziquantel, safe water supplies and use of toilets were deemed the most acceptable interventions by the participants. The communities are willing to participate in Schistosoma vaccine trials. CONCLUSION/SIGNIFICANCE: Knowledge of a community's perception about interventions to control schistosomiasis can be valuable to policy makers and programme implementers intending to set up interventions co-managed by the community members. In this study, the views of the Lake Victoria island communities of Koome are presented. This study also provides data to guide further work on alternative interventions such as Schistosoma vaccine trials in these communities.
[Mh] Termos MeSH primário: Conhecimentos, Atitudes e Prática em Saúde
Controle de Infecções/métodos
Esquistossomose mansoni/epidemiologia
Esquistossomose mansoni/prevenção & controle
[Mh] Termos MeSH secundário: Adulto
Animais
Água Potável/normas
Fezes/parasitologia
Feminino
Grupos Focais
Seres Humanos
Controle de Infecções/estatística & dados numéricos
Entrevistas como Assunto
Ilhas
Lagos
Vacinas contra Leishmaniose
Masculino
Meia-Idade
Praziquantel/uso terapêutico
Prevalência
Distribuição Espacial da População
Saneamento/normas
Schistosoma mansoni/isolamento & purificação
Esquistossomose mansoni/parasitologia
Esquistossomose mansoni/transmissão
Caramujos/parasitologia
Sanitários Públicos/normas
Sanitários Públicos/estatística & dados numéricos
Uganda/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Drinking Water); 0 (Leishmaniasis Vaccines); 6490C9U457 (Praziquantel)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171003
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005982


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[PMID]:28963929
[Au] Autor:Rostamian M; Niknam HM
[Ad] Endereço:Immunology Department, Pasteur Institute of Iran, Tehran, 13164, Iran.
[Ti] Título:Evaluation of the adjuvant effect of agonists of toll-like receptor 4 and 7/8 in a vaccine against leishmaniasis in BALB/c mice.
[So] Source:Mol Immunol;91:202-208, 2017 11.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:There is no effective vaccine against human leishmaniasis. Achieving successful vaccines seems to need powerful adjuvants. Separate or combined use of toll like receptor (TLR) agonists as adjuvant is a promising approach in Leishmania vaccine research. In present study, we evaluated adjuvant effect of separate or combined use of a TLR7/8 agonist, R848 and a TLR4 agonist, monophosphoryl lipid A (MPL) beside soluble Leishmania antigen (SLA) in BALB/c mice. Mice were vaccinated three times by SLA with separate or combined TLR7/8 and TLR4 agonists and were then challenged by Leishmania major. Delay type hypersensitivity, lesion development, parasite load, and cytokines (interferon gamma, and interleukin-10) response were assessed. Results showed: 1) MPL can slightly assist SLA in parasite load reduction, but it is not able to increase SLA ability in evoking DTH and cytokine responses or decreasing lesion diameter. 2) R848 does not affect the DTH response and parasite load of mice vaccinated with SLA, but it decreases/inhibits cytokine responses induced by SLA, leading to increase lesion diameter. 3) MPL neutralized inhibitory effect of R848. In overall, these data emphasize that MPL slightly assists SLA to make a more potent vaccine, but R848 is not a good adjuvant to induce T cell-dependent immune response in BALB/c mice, and therefore combination of these TLR agonists in the current formulation, is not recommended for making a more powerful adjuvant.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/farmacologia
Imidazóis/farmacologia
Leishmania major/imunologia
Vacinas contra Leishmaniose/farmacologia
Leishmaniose Cutânea/prevenção & controle
Lipídeo A/análogos & derivados
Glicoproteínas de Membrana/agonistas
Receptor 4 Toll-Like/agonistas
Receptor 7 Toll-Like/agonistas
Receptor 8 Toll-Like/agonistas
[Mh] Termos MeSH secundário: Animais
Antígenos de Protozoários/imunologia
Antígenos de Protozoários/farmacologia
Hipersensibilidade Tardia/imunologia
Hipersensibilidade Tardia/patologia
Imidazóis/imunologia
Interferon gama/imunologia
Interleucina-10/imunologia
Vacinas contra Leishmaniose/imunologia
Leishmaniose Cutânea/imunologia
Leishmaniose Cutânea/patologia
Lipídeo A/imunologia
Lipídeo A/farmacologia
Glicoproteínas de Membrana/imunologia
Camundongos
Camundongos Endogâmicos BALB C
Receptor 4 Toll-Like/imunologia
Receptor 7 Toll-Like/imunologia
Receptor 8 Toll-Like/imunologia
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antigens, Protozoan); 0 (IFNG protein, mouse); 0 (IL10 protein, mouse); 0 (Imidazoles); 0 (Leishmaniasis Vaccines); 0 (Lipid A); 0 (Membrane Glycoproteins); 0 (TLR8 protein, mouse); 0 (Tlr4 protein, mouse); 0 (Tlr7 protein, mouse); 0 (Toll-Like Receptor 4); 0 (Toll-Like Receptor 7); 0 (Toll-Like Receptor 8); 130068-27-8 (Interleukin-10); 82115-62-6 (Interferon-gamma); MWC0ET1L2P (monophosphoryl lipid A); V3DMU7PVXF (resiquimod)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171001
[St] Status:MEDLINE


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[PMID]:28953944
[Au] Autor:Grimaldi G; Teva A; Dos-Santos CB; Santos FN; Pinto ID; Fux B; Leite GR; Falqueto A
[Ad] Endereço:Instituto Gonçalo Moniz, Fiocruz, Salvador, Brazil, Brazil.
[Ti] Título:Field trial of efficacy of the Leish-tec® vaccine against canine leishmaniasis caused by Leishmania infantum in an endemic area with high transmission rates.
[So] Source:PLoS One;12(9):e0185438, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Because domestic dogs are reservoir hosts for visceral leishmaniasis (VL) in Brazil, one of the approaches used to reduce human disease incidence is to cull infected dogs. However, the results of controlled intervention trials based on serological screening of dogs and killing of seropositive animals are equivocal. A prophylactic vaccine to protect dogs from being infectious to the sand fly vector could be an effective strategy to provide sustained control. Here, we investigated whether a currently licensed commercial subunit rA2 protein-saponin vaccine (Leish-tec®) had an additional effect to dog culling on reducing the canine infectious populations. METHODOLOGY/PRINCIPAL FINDINGS: This prospective study was conducted in an L. infantum highly endemic area of southeast Brazil. At the onset of the intervention, all of the eligible dogs received through subcutaneous route a three-dose vaccine course at 21-day intervals and a booster on month 12. For the purpose of comparison, newly recruited healthy dogs were included as the exposed control group. To ascertain vaccine-induced protection, dogs were screened on clinical and serological criteria every 6 months for a 2-year follow-up period. Antibody-based tests and histopathological examination of post-mortem tissue specimens from euthanized animals were used as a marker of infection. The standardized vaccine regime, apart from being safe, was immunogenic as immunized animals responded with a pronounced production of anti-A2-specific IgG antibodies. It should be noted the mean seroconversion time for infection obtained among immunized exposed dogs (~ 18 months), which was twice as high as that for unvaccinated ones (~ 9 months). After two transmission cycles completed, the cumulative incidence of infection did differ significantly (P = 0.016) between the vaccinated (27%) and unvaccinated (42%) dogs. However, the expected efficacy for the vaccine in inducing clinical protection was not evident since 43% of vaccine recipients developed disease over time. Our estimates also indicated that immunoprophylaxis by Leish-tec® vaccine in addition to dog culling might not have an impact on bringing down the incidence of canine infection with L. infantum in areas of high transmission rates. CONCLUSIONS/SIGNIFICANCE: Leish-tec® as a prophylactic vaccine showed promise but needs to be further optimized to be effective in dogs under field conditions, and thereby positively impacts human incidence.
[Mh] Termos MeSH primário: Doenças do Cão/prevenção & controle
Leishmania infantum/isolamento & purificação
Vacinas contra Leishmaniose/uso terapêutico
Leishmaniose Visceral/veterinária
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/biossíntese
Brasil/epidemiologia
Progressão da Doença
Doenças do Cão/epidemiologia
Doenças do Cão/transmissão
Cães
Leishmania infantum/imunologia
Leishmaniose Visceral/epidemiologia
Leishmaniose Visceral/prevenção & controle
Leishmaniose Visceral/transmissão
Prevalência
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Leishmaniasis Vaccines)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170928
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0185438


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[PMID]:28689776
[Au] Autor:Solano-Gallego L; Cardoso L; Pennisi MG; Petersen C; Bourdeau P; Oliva G; Miró G; Ferrer L; Baneth G
[Ad] Endereço:Departament de Medicina i Cirurgia Animals, Facultat de Veterinària, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain. Electronic address: laia.solano@uab.cat.
[Ti] Título:Diagnostic Challenges in the Era of Canine Leishmania infantum Vaccines.
[So] Source:Trends Parasitol;33(9):706-717, 2017 09.
[Is] ISSN:1471-5007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The diagnosis of canine leishmaniosis (CanL) is complex due to its variable clinical manifestations and laboratory findings. The availability of vaccines to prevent CanL has increased the complexity of diagnosis, as serological tests may not distinguish between naturally infected and vaccinated dogs. Current practices of prevaccination screening are not sufficiently sensitive to detect subclinically infected dogs, resulting in the vaccination of infected animals, which may lead to disease in vaccinated dogs that are also infectious to sand flies. This review evaluates the current techniques for diagnosing CanL, and focuses on new challenges raised by the increasing use of vaccines against this disease. Important gaps in knowledge regarding the diagnosis of CanL are underscored to highlight the need for novel diagnostic test development.
[Mh] Termos MeSH primário: Doenças do Cão/diagnóstico
Leishmaniose/veterinária
[Mh] Termos MeSH secundário: Animais
Cães
Leishmania infantum/imunologia
Leishmaniose/diagnóstico
Vacinas contra Leishmaniose/imunologia
Testes Sorológicos/normas
Testes Sorológicos/veterinária
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Leishmaniasis Vaccines)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171121
[Lr] Data última revisão:
171121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE


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[PMID]:28498840
[Au] Autor:Osman M; Mistry A; Keding A; Gabe R; Cook E; Forrester S; Wiggins R; Di Marco S; Colloca S; Siani L; Cortese R; Smith DF; Aebischer T; Kaye PM; Lacey CJ
[Ad] Endereço:Centre for Immunology and Infection, Dept. of Biology and Hull York Medical School, University of York, Heslington, York, United Kingdom.
[Ti] Título:A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.
[So] Source:PLoS Negl Trop Dis;11(5):e0005527, 2017 May.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359).
[Mh] Termos MeSH primário: Vacinas contra Leishmaniose/imunologia
Vacinas contra Leishmaniose/isolamento & purificação
Leishmaniose Cutânea/prevenção & controle
Leishmaniose Cutânea/terapia
Leishmaniose Visceral/prevenção & controle
Leishmaniose Visceral/terapia
[Mh] Termos MeSH secundário: Adenovirus dos Símios/genética
Adolescente
Adulto
Antígenos de Protozoários/genética
Antígenos de Protozoários/imunologia
Linfócitos T CD8-Positivos/imunologia
Portadores de Fármacos
ELISPOT
Feminino
Citometria de Fluxo
Voluntários Saudáveis
Seres Humanos
Injeções Intramusculares
Interferon gama/secreção
Leishmania/genética
Leishmania/imunologia
Vacinas contra Leishmaniose/administração & dosagem
Vacinas contra Leishmaniose/efeitos adversos
Masculino
Meia-Idade
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/efeitos adversos
Vacinas Sintéticas/imunologia
Vacinas Sintéticas/isolamento & purificação
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE I; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Protozoan); 0 (Drug Carriers); 0 (Leishmaniasis Vaccines); 0 (Vaccines, Synthetic); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170713
[Lr] Data última revisão:
170713
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170513
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005527


  9 / 304 MEDLINE  
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[PMID]:28426153
[Au] Autor:Pirdel L; Farajnia S
[Ad] Endereço:Department of Medical Sciences, Ardabil Branch, Islamic Azad University, Ardabil, Iran.
[Ti] Título:A Non-pathogenic Recombinant Leishmania Expressing Lipophosphoglycan 3 Against Experimental Infection with Leishmania infantum.
[So] Source:Scand J Immunol;86(1):15-22, 2017 Jul.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Visceral leishmaniasis (VL) is caused by Leishmania infantum in the Mediterranean basin and affects primarily children and immunosuppressed individuals. Various strategies of vaccination have so far been examined by either protein or DNA without achievable complete protection against the disease. The live non-pathogenic lizard parasite, Leishmania tarentolae, expressing elected Leishmania antigens has recently provided a promising new approach as a safe and effective live vaccine candidate to prevent leishmaniasis. Here, we evaluated the immunoprotective potential of a live recombinant L. tarentolae expressing Lipophosphoglycan 3 (LPG3) antigen against L. infantum infection in BALB/c mice. Results indicated that the administration of live recombinant Leishmania produced a significant high level of IFN-γ accompanied by reduced levels of IL-10 as compared to wild-type parasites as live vaccine control, thus suggesting the induction of a Th1-type immune response in a mouse model of visceral leishmaniasis. Analysis of the IgG antibody response also showed high levels of IgG2a relative to IgG1 in sera of mice immunized with recombinant Leishmania parasites. However, immune responses elicited by this live vaccine conferred partial protection against infectious challenge. Therefore, further studies are required to increase its protective efficacy.
[Mh] Termos MeSH primário: Leishmania infantum/imunologia
Vacinas contra Leishmaniose/imunologia
Leishmaniose Visceral/imunologia
Proteínas de Protozoários/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/sangue
Anticorpos Antiprotozoários/imunologia
Ensaio de Imunoadsorção Enzimática
Feminino
Imunoglobulina G/sangue
Imunoglobulina G/imunologia
Interferon gama/imunologia
Interferon gama/metabolismo
Interleucina-10/imunologia
Interleucina-10/metabolismo
Leishmania infantum/fisiologia
Vacinas contra Leishmaniose/administração & dosagem
Leishmaniose Visceral/parasitologia
Leishmaniose Visceral/prevenção & controle
Camundongos Endogâmicos BALB C
Proteínas de Protozoários/administração & dosagem
Proteínas de Protozoários/genética
Proteínas Recombinantes/administração & dosagem
Proteínas Recombinantes/imunologia
Baço/efeitos dos fármacos
Baço/imunologia
Baço/parasitologia
Resultado do Tratamento
Vacinação/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Immunoglobulin G); 0 (Leishmaniasis Vaccines); 0 (Protozoan Proteins); 0 (Recombinant Proteins); 130068-27-8 (Interleukin-10); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12557


  10 / 304 MEDLINE  
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Texto completo
[PMID]:28249007
[Au] Autor:Moraes-Souza RQ; Reinaque AP; Soares TS; Silva AL; Giunchetti RC; Takano MA; Akamatsu MA; Kubrusly FS; Lúcio-Macarini F; Raw I; Iourtov D; Ho PL; Bueno LL; Fujiwara RT; Volpato GT
[Ad] Endereço:Laboratory of System Physiology and Reproductive Toxicology, Institute of Biological and Health Sciences, Federal University of Mato Grosso (UFMT) - Barra do Garças, Mato Grosso State, Brazil.
[Ti] Título:Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model.
[So] Source:PLoS One;12(3):e0172525, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control-rats received saline; Adjuvant-rats received the adjuvant MPLA, and Vaccine-rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy.
[Mh] Termos MeSH primário: Perda do Embrião/induzido quimicamente
Feto/anormalidades
Leishmania braziliensis
Vacinas contra Leishmaniose/efeitos adversos
Exposição Materna/efeitos adversos
Modelos Biológicos
Peroxirredoxinas/efeitos adversos
Proteínas de Protozoários/efeitos adversos
[Mh] Termos MeSH secundário: Animais
Anticorpos Antiprotozoários/imunologia
Avaliação Pré-Clínica de Medicamentos
Feminino
Feto/imunologia
Imunoglobulina G/imunologia
Vacinas contra Leishmaniose/imunologia
Vacinas contra Leishmaniose/farmacologia
Peroxirredoxinas/imunologia
Peroxirredoxinas/farmacologia
Gravidez
Proteínas de Protozoários/imunologia
Proteínas de Protozoários/farmacologia
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (Immunoglobulin G); 0 (Leishmaniasis Vaccines); 0 (Protozoan Proteins); EC 1.11.1.15 (Peroxiredoxins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170302
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172525



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