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  1 / 712 MEDLINE  
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[PMID]:29028799
[Au] Autor:Kracalik IT; Kenu E; Ayamdooh EN; Allegye-Cudjoe E; Polkuu PN; Frimpong JA; Nyarko KM; Bower WA; Traxler R; Blackburn JK
[Ad] Endereço:Spatial Epidemiology & Ecology Research Laboratory, Department of Geography, University of Florida, Gainesville, FL, United States of America.
[Ti] Título:Modeling the environmental suitability of anthrax in Ghana and estimating populations at risk: Implications for vaccination and control.
[So] Source:PLoS Negl Trop Dis;11(10):e0005885, 2017 Oct.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Anthrax is hyper-endemic in West Africa. Despite the effectiveness of livestock vaccines in controlling anthrax, underreporting, logistics, and limited resources makes implementing vaccination campaigns difficult. To better understand the geographic limits of anthrax, elucidate environmental factors related to its occurrence, and identify human and livestock populations at risk, we developed predictive models of the environmental suitability of anthrax in Ghana. We obtained data on the location and date of livestock anthrax from veterinary and outbreak response records in Ghana during 2005-2016, as well as livestock vaccination registers and population estimates of characteristically high-risk groups. To predict the environmental suitability of anthrax, we used an ensemble of random forest (RF) models built using a combination of climatic and environmental factors. From 2005 through the first six months of 2016, there were 67 anthrax outbreaks (851 cases) in livestock; outbreaks showed a seasonal peak during February through April and primarily involved cattle. There was a median of 19,709 vaccine doses [range: 0-175 thousand] administered annually. Results from the RF model suggest a marked ecological divide separating the broad areas of environmental suitability in northern Ghana from the southern part of the country. Increasing alkaline soil pH was associated with a higher probability of anthrax occurrence. We estimated 2.2 (95% CI: 2.0, 2.5) million livestock and 805 (95% CI: 519, 890) thousand low income rural livestock keepers were located in anthrax risk areas. Based on our estimates, the current anthrax vaccination efforts in Ghana cover a fraction of the livestock potentially at risk, thus control efforts should be focused on improving vaccine coverage among high risk groups.
[Mh] Termos MeSH primário: Vacinas contra Antraz
Antraz/epidemiologia
Antraz/veterinária
Surtos de Doenças/veterinária
Gado
[Mh] Termos MeSH secundário: Algoritmos
Animais
Antraz/microbiologia
Antraz/prevenção & controle
Bacillus anthracis/isolamento & purificação
Bovinos
Doenças dos Bovinos/microbiologia
Doenças dos Bovinos/prevenção & controle
Clima
Simulação por Computador
Meio Ambiente
Métodos Epidemiológicos
Gana/epidemiologia
Seres Humanos
Concentração de Íons de Hidrogênio
Gado/microbiologia
Fatores de Risco
Solo/química
Vacinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Soil)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005885


  2 / 712 MEDLINE  
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[PMID]:28736824
[Au] Autor:Wei Y; Wahome N; VanSlyke G; Whitaker N; Kumar P; Barta ML; Picking WL; Volkin DB; Mantis NJ; Middaugh CR
[Ad] Endereço:Macromolecule and Vaccine Stabilization Center, Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas, 66047.
[Ti] Título:Evaluation of lumazine synthase from Bacillus anthracis as a presentation platform for polyvalent antigen display.
[So] Source:Protein Sci;26(10):2059-2072, 2017 Oct.
[Is] ISSN:1469-896X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Polyvalent antigen display is an effective strategy to enhance the immunogenicity of subunit vaccines by clustering them in an array-like manner on a scaffold system. This strategy results in a higher local density of antigens, increased high avidity interactions with B cells and other antigen presenting cells, and therefore a more effective presentation of vaccine antigens. In this study, we used lumazine synthase (LS), an icosahedral symmetry capsid derived from Bacillus anthracis, as a scaffold to present 60 copies of a linear B cell epitope (PB10) from the ricin toxin fused to the C terminus of LS via four different linkers. We then investigated the effects of linker length, linker rigidity and formaldehyde crosslinking on the protein assembly, conformational integrity, thermal stability, in vitro antibody binding, and immunogenicity in mice. Fusion of the PB10 peptide onto LS, with varying linker lengths, did not affect protein assembly, thermal stability or exposure of the epitope, but had a minor impact on protein conformation. Formaldehyde crosslinking considerably improved protein thermal stability with only minor impact on protein conformation. All LS_PB10 constructs, when administered to mice by injection without adjuvant, elicited measurable anti-ricin serum IgG titers, although the titers were not sufficient to confer protection against a 10× lethal dose ricin challenge. This work sheds light on the biophysical properties, immunogenicity and potential feasibility of LS from B. anthracis as a scaffold system for polyvalent antigen display.
[Mh] Termos MeSH primário: Vacinas contra Antraz
Antígenos de Bactérias
Bacillus anthracis
Epitopos de Linfócito B
Complexos Multienzimáticos
Vacinas de Subunidades
[Mh] Termos MeSH secundário: Animais
Vacinas contra Antraz/química
Vacinas contra Antraz/genética
Vacinas contra Antraz/imunologia
Vacinas contra Antraz/metabolismo
Anticorpos Antibacterianos/sangue
Anticorpos Antibacterianos/imunologia
Antígenos de Bactérias/química
Antígenos de Bactérias/genética
Antígenos de Bactérias/imunologia
Antígenos de Bactérias/metabolismo
Bacillus anthracis/enzimologia
Bacillus anthracis/imunologia
Epitopos de Linfócito B/química
Epitopos de Linfócito B/genética
Epitopos de Linfócito B/imunologia
Epitopos de Linfócito B/metabolismo
Feminino
Imunoglobulina G/sangue
Imunoglobulina G/imunologia
Camundongos
Modelos Moleculares
Complexos Multienzimáticos/química
Complexos Multienzimáticos/genética
Complexos Multienzimáticos/imunologia
Complexos Multienzimáticos/metabolismo
Estabilidade Proteica
Ricina/química
Ricina/genética
Ricina/imunologia
Ricina/metabolismo
Vacinas de Subunidades/química
Vacinas de Subunidades/genética
Vacinas de Subunidades/imunologia
Vacinas de Subunidades/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Antibodies, Bacterial); 0 (Antigens, Bacterial); 0 (Epitopes, B-Lymphocyte); 0 (Immunoglobulin G); 0 (Multienzyme Complexes); 0 (Vaccines, Subunit); 89287-46-7 (6,7-dimethyl-8-ribityllumazine synthase); 9009-86-3 (Ricin)
[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:170725
[St] Status:MEDLINE
[do] DOI:10.1002/pro.3243


  3 / 712 MEDLINE  
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[PMID]:28662082
[Au] Autor:Weir GM; Karkada M; Hoskin D; Stanford MM; MacDonald L; Mansour M; Liwski RS
[Ad] Endereço:Research & Development, Immunovaccine Inc, Halifax, Nova Scotia, Canada.
[Ti] Título:Combination of poly I:C and Pam3CSK4 enhances activation of B cells in vitro and boosts antibody responses to protein vaccines in vivo.
[So] Source:PLoS One;12(6):e0180073, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vaccines that can rapidly induce strong and robust antibody-mediated immunity could improve protection from certain infectious diseases for which current vaccine formulations are inefficient. For indications such as anthrax and influenza, antibody production in vivo is a correlate of efficacy. Toll-like receptor (TLR) agonists are frequently studied for their role as vaccine adjuvants, largely because of their ability to enhance initiation of immune responses to antigens by activating dendritic cells. However, TLRs are also expressed on B cells and may contribute to effective B cell activation and promote differentiation into antigen-specific antibody producing plasma cells in vivo. We sought to discover an adjuvant system that could be used to augment antibody responses to influenza and anthrax vaccines. We first characterized an adjuvant system in vitro which consisted of two TLR ligands, poly I:C (TLR3) and Pam3CSK4 (TLR2), by evaluating its effects on B cell activation. Each agonist enhanced B cell activation through increased expression of surface receptors, cytokine secretion and proliferation. However, when B cells were stimulated with poly I:C and Pam3CSK4 in combination, further enhancement to cell activation was observed. Using B cells isolated from knockout mice we confirmed that poly I:C and Pam3CSK4 were signaling through TLR3 and TLR2, respectively. B cells activated with Poly I:C and Pam3CSK4 displayed enhanced capacity to stimulate allogeneic CD4+ T cell activation and differentiate into antibody-producing plasma cells in vitro. Mice vaccinated with influenza or anthrax antigens formulated with poly I:C and Pam3CSK4 in DepoVax™ vaccine platform developed a rapid and strong antigen-specific serum antibody titer that persisted for at least 12 weeks after a single immunization. These results demonstrate that combinations of TLR adjuvants promote more effective B cell activation in vitro and can be used to augment antibody responses to vaccines in vivo.
[Mh] Termos MeSH primário: Vacinas contra Antraz/imunologia
Anticorpos Antibacterianos/biossíntese
Anticorpos Antivirais/biossíntese
Linfócitos B/efeitos dos fármacos
Vacinas contra Influenza/imunologia
Lipopeptídeos/farmacologia
Ativação Linfocitária/efeitos dos fármacos
Poli I-C/farmacologia
[Mh] Termos MeSH secundário: Animais
Linfócitos B/imunologia
Quimioterapia Combinada
Feminino
Técnicas In Vitro
Lipopeptídeos/administração & dosagem
Camundongos
Camundongos Endogâmicos
Camundongos Knockout
Poli I-C/administração & dosagem
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Antibodies, Bacterial); 0 (Antibodies, Viral); 0 (Influenza Vaccines); 0 (Lipopeptides); 0 (Pam(3)CSK(4) peptide); O84C90HH2L (Poly I-C)
[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:170630
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180073


  4 / 712 MEDLINE  
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[PMID]:28215694
[Au] Autor:Lv J; Zhang YY; Lu X; Zhang H; Wei L; Gao J; Hu B; Hu WW; Hu DZ; Jia N; Feng X
[Ad] Endereço:The General Hospital of the PLA Rocket Force, Beijing, China.
[Ti] Título:Comparisons of the humoral and cellular immunity induced by live A16R attenuated spore and AVA-like anthrax vaccine in mice.
[So] Source:Biologicals;46:130-138, 2017 Mar.
[Is] ISSN:1095-8320
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The live attenuated anthrax vaccine and anthrax vaccine adsorbed (AVA) are two main types of anthrax vaccines currently used in human. However, the immunoprotective mechanisms are not fully understood. In this study, we compared humoral and cellular immunity induced by live A16R spore vaccine and A16R strain derived AVA-like vaccine in mice peripheral blood, spleen and bone marrow. Both A16R spores and AVA-like vaccines induced a sustained IgG antibody response with IgG1/IgG2b subtype dominance. However, A16R spores vaccine induced higher titer of IgG2a compared with AVA-like vaccine, indicating a stronger Th1 response to A16R spores. Using antigen-specific ELISpot assay, we observed a significant response of ASCs (antibody secreting cells) and IL4-CSCs (cytokine secreting cells) in mice. Specially, there was a positive correlation between the frequencies of antigen specific ASCs and IL4-CSCs in bone marrow derived cells, either by A16R spore or AVA-like vaccine vaccination. Moreover, we also found A16R spore vaccine, not AVA-like vaccine, could induce sustained frequency of IFN-γ-CSCs in bone marrow derived cells. Collectively, both the vaccines induced a mixed Th1/Th2 response with Th2 dominance in mice and A16R spore vaccine might provide a more comprehensive protection because of humoral and cellular immunity induced in bone marrow.
[Mh] Termos MeSH primário: Vacinas contra Antraz/imunologia
Antraz/imunologia
Bacillus anthracis/imunologia
Imunidade Celular/imunologia
Imunidade Humoral/imunologia
[Mh] Termos MeSH secundário: Animais
Antraz/microbiologia
Antraz/prevenção & controle
Anticorpos Antibacterianos/imunologia
Células da Medula Óssea/imunologia
Células da Medula Óssea/metabolismo
Células Cultivadas
Citocinas/imunologia
Citocinas/metabolismo
Ensaio de Imunoadsorção Enzimática
ELISPOT
Feminino
Imunização
Imunoglobulina G/imunologia
Leucócitos Mononucleares/imunologia
Leucócitos Mononucleares/metabolismo
Camundongos Endogâmicos BALB C
Baço/citologia
Baço/imunologia
Baço/metabolismo
Esporos Bacterianos/imunologia
Células Th1/imunologia
Células Th2/imunologia
Vacinação/métodos
Vacinas Atenuadas/imunologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Antibodies, Bacterial); 0 (Cytokines); 0 (Immunoglobulin G); 0 (Vaccines, Attenuated)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170418
[Lr] Data última revisão:
170418
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170221
[St] Status:MEDLINE


  5 / 712 MEDLINE  
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[PMID]:28056004
[Au] Autor:Allen KC; Hendricks K; Sergienko E; Mirza R; Chitale RA
[Ti] Título:Notes from the Field: Compliance with Postexposure Prophylaxis for Exposure to Bacillus anthracis Among U.S. Military Personnel - South Korea, May 2015.
[So] Source:MMWR Morb Mortal Wkly Rep;65(52):1489-1490, 2017 Jan 06.
[Is] ISSN:1545-861X
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Antraz/prevenção & controle
Bacillus anthracis
Militares/psicologia
Cooperação do Paciente/estatística & dados numéricos
Profilaxia Pós-Exposição/utilização
[Mh] Termos MeSH secundário: Amoxicilina/uso terapêutico
Vacinas contra Antraz/administração & dosagem
Antibacterianos/uso terapêutico
Ciprofloxacino/uso terapêutico
Estudos de Coortes
Doxiciclina/uso terapêutico
Feminino
Seres Humanos
Masculino
Militares/estatística & dados numéricos
Gravidez
República da Coreia
Estados Unidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Anti-Bacterial Agents); 5E8K9I0O4U (Ciprofloxacin); 804826J2HU (Amoxicillin); N12000U13O (Doxycycline)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170119
[Lr] Data última revisão:
170119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170106
[St] Status:MEDLINE
[do] DOI:10.15585/mmwr.mm6552a7


  6 / 712 MEDLINE  
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[PMID]:28035484
[Au] Autor:Saad-Roy CM; van den Driessche P; Yakubu AA
[Ad] Endereço:Department of Mathematics and Statistics, University of Victoria, Victoria, BC, V8W 2Y2, Canada. saadroy@uvic.ca.
[Ti] Título:A Mathematical Model of Anthrax Transmission in Animal Populations.
[So] Source:Bull Math Biol;79(2):303-324, 2017 Feb.
[Is] ISSN:1522-9602
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A general mathematical model of anthrax (caused by Bacillus anthracis) transmission is formulated that includes live animals, infected carcasses and spores in the environment. The basic reproduction number [Formula: see text] is calculated, and existence of a unique endemic equilibrium is established for [Formula: see text] above the threshold value 1. Using data from the literature, elasticity indices for [Formula: see text] and type reproduction numbers are computed to quantify anthrax control measures. Including only herbivorous animals, anthrax is eradicated if [Formula: see text]. For these animals, oscillatory solutions arising from Hopf bifurcations are numerically shown to exist for certain parameter values with [Formula: see text] and to have periodicity as observed from anthrax data. Including carnivores and assuming no disease-related death, anthrax again goes extinct below the threshold. Local stability of the endemic equilibrium is established above the threshold; thus, periodic solutions are not possible for these populations. It is shown numerically that oscillations in spore growth may drive oscillations in animal populations; however, the total number of infected animals remains about the same as with constant spore growth.
[Mh] Termos MeSH primário: Antraz/veterinária
Modelos Biológicos
[Mh] Termos MeSH secundário: Animais
Antraz/microbiologia
Antraz/transmissão
Vacinas contra Antraz/farmacologia
Bacillus anthracis/crescimento & desenvolvimento
Bacillus anthracis/patogenicidade
Número Básico de Reprodução
Carnivoridade
Herbivoria
Seres Humanos
Gado
Conceitos Matemáticos
Dinâmica Populacional
Esporos Bacterianos/crescimento & desenvolvimento
Esporos Bacterianos/patogenicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170925
[Lr] Data última revisão:
170925
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.1007/s11538-016-0238-1


  7 / 712 MEDLINE  
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[PMID]:27792416
[Au] Autor:Longstreth J; Skiadopoulos MH; Hopkins RJ
[Ad] Endereço:a Biodefense Division , Emergent BioSolutions Inc ., Gaithersburg , MD , US.
[Ti] Título:Licensure strategy for pre- and post-exposure prophylaxis of biothrax vaccine: the first vaccine licensed using the FDA animal rule.
[So] Source:Expert Rev Vaccines;15(12):1467-1479, 2016 Dec.
[Is] ISSN:1744-8395
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: The availability of a licensed anthrax vaccine that is safe, effective, and easy to administer for both pre- and post-exposure prophylaxis is critical to successfully manage and prevent potential anthrax attacks. BioThrax® (Anthrax Vaccine Adsorbed; AVA) is the only licensed anthrax vaccine in the US. Areas covered: Recent licensed improvements to BioThrax vaccine for pre-exposure prophylaxis (PrEP) have included an intramuscular (IM) five-dose schedule (in 2008) and a three-dose IM primary series at 0, 1 and 6 months (in 2012). Post-exposure prophylaxis (PEP) - three doses given subcutaneously (SC) at 0, 2, and 4 weeks - was licensed in 2015. We review the anthrax disease and vaccine literature that supported these licensure efforts. Expert commentary: This PEP licensure is the first time the FDA's Animal Rule has been used to license a vaccine. Additional improvements such as fewer vaccine doses and reduced time to protection are desirable for a PEP vaccine and are being pursued with next generation vaccine candidates.
[Mh] Termos MeSH primário: Vacinas contra Antraz/administração & dosagem
Vacinas contra Antraz/imunologia
Antraz/prevenção & controle
Aprovação de Drogas
Profilaxia Pós-Exposição/métodos
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Esquemas de Imunização
Injeções Intramusculares
Injeções Subcutâneas
Estados Unidos
United States Food and Drug Administration
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Biothrax)
[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:161030
[St] Status:MEDLINE


  8 / 712 MEDLINE  
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[PMID]:27753574
[Au] Autor:Bardenheier BH; Duffy J; Duderstadt SK; Higgs JB; Keith MP; Papadopoulos PJ; Gilliland WR; McNeil MM
[Ad] Endereço:Immunization Safety Office, MS D-26, 1600 Clifton Road NE, Centers for Disease Control and Prevention, Atlanta, GA 30333.
[Ti] Título:Anthrax Vaccine and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus in the U.S. Military: A Case-Control Study.
[So] Source:Mil Med;181(10):1348-1356, 2016 Oct.
[Is] ISSN:1930-613X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:U.S. military personnel assigned to areas deemed to be at high risk for anthrax attack receive Anthrax Vaccine Adsorbed (AVA). Few cases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have been reported in persons who received AVA. Using a matched case-control study design, we assessed the relationship of RA and SLE with AVA vaccination using the Defense Medical Surveillance System. We identified potential cases using International Classification of Diseases, 9th Revision, Clinical Modification codes and confirmed cases with medical record review and rheumatologist adjudication. Using conditional logistic regression, we estimated odds ratios (OR) for AVA exposure during time intervals ranging from 90 to 1,095 days before disease onset. Among 77 RA cases, 13 (17%) had ever received AVA. RA cases were no more likely than controls to have received AVA when looking back 1,095 days (OR: 1.03; 95% confidence interval [CI]: 0.48-2.19) but had greater odds of exposure in the prior 90 days (OR: 3.93; 95% CI: 1.08-14.27). Among the 39 SLE cases, 5 (13%) had ever received AVA; no significant difference in receipt of AVA was found when compared with controls (OR: 0.91; 95% CI: 0.26-3.25). AVA was associated with recent onset RA, but did not increase the risk of developing RA in the long term.
[Mh] Termos MeSH primário: Vacinas contra Antraz/efeitos adversos
Artrite Reumatoide/etiologia
Lúpus Eritematoso Sistêmico/etiologia
Militares/estatística & dados numéricos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Antraz/prevenção & controle
Vacinas contra Antraz/uso terapêutico
Estudos de Casos e Controles
Feminino
Seres Humanos
Modelos Logísticos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines)
[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:161019
[St] Status:MEDLINE


  9 / 712 MEDLINE  
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[PMID]:27647868
[Au] Autor:Balderas MA; Nguyen CT; Terwilliger A; Keitel WA; Iniguez A; Torres R; Palacios F; Goulding CW; Maresso AW
[Ad] Endereço:Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
[Ti] Título:Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease.
[So] Source:Infect Immun;84(12):3408-3422, 2016 Dec.
[Is] ISSN:1098-5522
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine.
[Mh] Termos MeSH primário: Vacinas contra Antraz/imunologia
Antraz/prevenção & controle
Proteínas de Bactérias/imunologia
[Mh] Termos MeSH secundário: Animais
Vacinas contra Antraz/administração & dosagem
Anticorpos Antibacterianos/sangue
Bacillus anthracis
Proteínas de Transporte/genética
Proteínas de Transporte/metabolismo
Clonagem Molecular
Injeções Intramusculares
Camundongos
Modelos Moleculares
Fagócitos
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Antibodies, Bacterial); 0 (Bacterial Proteins); 0 (Carrier Proteins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160921
[St] Status:MEDLINE


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[PMID]:27496738
[Au] Autor:Ndumnego OC; Köhler SM; Crafford J; van Heerden H; Beyer W
[Ad] Endereço:Department of Veterinary Tropical Diseases, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, 0110, Pretoria, South Africa. Electronic address: okeyndumnego@gmail.com.
[Ti] Título:Comparative analysis of the immunologic response induced by the Sterne 34F2 live spore Bacillus anthracis vaccine in a ruminant model.
[So] Source:Vet Immunol Immunopathol;178:14-21, 2016 Oct 01.
[Is] ISSN:1873-2534
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The Sterne 34F2 live spore vaccine (SLSV) developed in 1937 is the most widely used veterinary vaccine against anthrax. However, literature on the immunogenicity of this vaccine in a target ruminant host is scarce. In this study, we evaluated the humoral response to the Bacillus anthracis protective antigen (rPA), a recombinant bacillus collagen-like protein of anthracis (rBclA), formaldehyde inactivated spores (FIS) prepared from strain 34F2 and a vegetative antigen formulation prepared from a capsule and toxin deficient strain (CDC 1014) in Boer goats. The toxin neutralizing ability of induced antibodies was evaluated using an in vitro toxin neutralization assay. The protection afforded by the vaccine was also assessed in vaccinates. Anti-rPA, anti-FIS and lethal toxin neutralizing titres were superior after booster vaccinations, compared to single vaccinations. Qualitative analysis of humoral responses to rPA, rBclA and FIS antigens revealed a preponderance of anti-FIS IgG titres following either single or double vaccinations with the SLSV. Antibodies against FIS and rPA both increased by 350 and 300-fold following revaccinations respectively. There was no response to rBclA following vaccinations with the SLSV. Toxin neutralizing titres increased by 80-fold after single vaccination and 700-fold following a double vaccination. Lethal challenge studies in naïve goats indicated a minimum infective dose of 36 B. anthracis spores. Single and double vaccination with the SLSV protected 4/5 and 3/3 of goats challenged with>800 spores respectively. An early booster vaccination following the first immunization is suggested in order to achieve a robust immunity. Results from this study indicate that this crucial second vaccination can be administered as early as 3 months after the initial vaccination.
[Mh] Termos MeSH primário: Vacinas contra Antraz/uso terapêutico
Antraz/veterinária
Bacillus anthracis/imunologia
Doenças das Cabras/imunologia
Doenças das Cabras/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Antraz/imunologia
Antraz/prevenção & controle
Vacinas contra Antraz/administração & dosagem
Vacinas contra Antraz/imunologia
Anticorpos Antibacterianos/sangue
Anticorpos Neutralizantes/sangue
Antígenos de Bactérias/imunologia
Bacillus anthracis/patogenicidade
Toxinas Bacterianas/imunologia
Feminino
Cabras
Imunização Secundária/veterinária
Camundongos
Camundongos Endogâmicos BALB C
Esporos Bacterianos/imunologia
Esporos Bacterianos/patogenicidade
Virulência/imunologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anthrax Vaccines); 0 (Antibodies, Bacterial); 0 (Antibodies, Neutralizing); 0 (Antigens, Bacterial); 0 (Bacterial Toxins); 0 (anthrax toxin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170410
[Lr] Data última revisão:
170410
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160807
[St] Status:MEDLINE



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