Cross-protective immunity to Leishmania amazonensis is mediated by CD4+and CD8+epitopes of Leishmania donovani nucleoside hydrolase terminal domains

The nucleoside hydrolase (NH) of Leishmania donovani (NH36) is a phylogenetic marker of high homology among Leishmania parasites. in mice and dog vaccination, NH36 induces a CD4+ T cell-driven protective response against Leishmania chagasi infection directed against its C-terminal domain (F3). the C-terminal and N-terminal domain vaccines also decreased the footpad lesion caused by Leishmania amazonensis. We studied the basis of the crossed immune response using recombinant generated peptides covering the whole NH36 sequence and saponin for mice prophylaxis against L. amazonensis. the F1 (amino acids 1-103) and F3 peptide (amino acids 199-314) vaccines enhanced the IgG and IgG2a anti-NH36 antibodies to similar levels. the F3 vaccine induced the strongest DTH response, the highest proportions of NH36-specific CD4+ and CD8+ T cells after challenge and the highest expression of IFN-gamma and TNF-alpha. the F1 vaccine, on the other hand, induced a weaker but significant DTH response and a mild enhancement of IFN-gamma and TNF-alpha levels. the in vivo depletion with anti-CD4 or CD8 monoclonal antibodies disclosed that cross-protection against L. amazonensis infection was mediated by a CD4+ T cell response directed against the C-terminal domain (75% of reduction of the size of footpad lesion) followed by a CD8+T cell response against the N-terminal domain of NH36 (57% of reduction of footpad lesions). Both vaccines were capable of inducing long-term cross-immunity. the amino acid sequence of NH36 showed 93% identity to the sequence of the NH A34480 of L amazonensis, which also showed the presence of completely conserved predicted epitopes for CD4+ and CD8+ T cells in F1 domain, and of CD4+ epitopes differing by a single amino acid, in F1 and F3 domains. the identification of the C-terminal and N-terminal domains as the targets of the immune response to NH36 in the model of L. amazonensis infection represents a basis for the rationale development of a bivalent vaccine against leishmaniasis.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Univ Fed Rio de Janeiro, Inst Microbiol Paulo Goes, Dept Microbiol Geral, Lab Biol & Bioquim Leishmania, BR-21941902 Rio de Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Paulo Goes, Lab Imunol, BR-21941902 Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Belo Horizonte, MG, BrazilUniv Fed Rio de Janeiro, Fac Med, Programa Pos Grad Clin Med, BR-21941902 Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Terapia Celular & Mol, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Terapia Celular & Mol, Dept Microbiol Imunol & Parasitol, São Paulo, BrazilCNPq: 301215-2007-3CNPq: 302039/2010-4CNPq: 559756/2010-0CNPq: 404400/2012-4FAPERJ: 102733/2008FAPERJ: 102957/2011FAPERJ: E-26/102415/2010FAPERJ: E-26/110535/2010Web of Scienc

Vaccines for Canine Leishmaniasis

Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL

Small RNA Profile in Moso Bamboo Root and Leaf Obtained by High Definition Adapters

Moso bamboo (Phyllostachy heterocycla cv. pubescens L.) is an economically important fast-growing tree. In order to gain better understanding of gene expression regulation in this important species we used next generation sequencing to profile small RNAs in leaf and roots of young seedlings. Since standard kits to produce cDNA of small RNAs are biased for certain small RNAs, we used High Definition adapters that reduce ligation bias. We identified and experimentally validated five new microRNAs and a few other small non-coding RNAs that were not microRNAs. The biological implication of microRNA expression levels and targets of microRNAs are discussed

Strain-induced partially flat band, helical snake states, and interface superconductivity in topological crystalline insulators

Topological crystalline insulators in IV-VI compounds host novel topological surface states consisting of multi-valley massless Dirac fermions at low energy. Here we show that strain generically acts as an effective gauge field on these Dirac fermions and creates pseudo-Landau orbitals without breaking time-reversal symmetry. We predict the realization of this phenomenon in IV-VI semiconductor heterostructures, due to a naturally occurring misfit dislocation array at the interface that produces a periodically varying strain field. Remarkably, the zero-energy Landau orbitals form a flat band in the vicinity of the Dirac point, and coexist with a network of snake states at higher energy. We propose that the high density of states of this flat band gives rise to interface superconductivity observed in IV-VI semiconductor multilayers at unusually high temperatures, with non-BCS behavior. Our work demonstrates a new route to altering macroscopic electronic properties to achieve a partially flat band, and paves the way for realizing novel correlated states of matter.Comment: Accepted by Nature Physic

Non-Abelian Einstein-Born-Infeld Black Holes

We construct regular and black hole solutions in SU(2) Einstein-Born-Infeld theory. These solutions have many features in common with the corresponding SU(2) Einstein-Yang-Mills solutions. In particular, sequences of neutral non-abelian solutions tend to magnetically charged limiting solutions, related to embedded abelian solutions. Thermodynamic properties of the black hole solutions are addressed.Comment: LaTeX, 14 pages, 6 postscript figures; typos corrected in reference

Influence of boric anhydride upon the physical and chemical properties of ferrosilicon slag

The authors study the influence of boric anhydride upon the physical and chemical properties of slag in the manufacture of ferrosilicon. It is established that adding boric anhydride to the slag changes its refractory quality and its viscosity and eases pouring slag and metal. Slags with optimal composition and properties are described

The Reactome pathway knowledgebase

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation

Processo e composição farmacêutica imunoquimioterápica para tratamento de leishmaníase canina e humana

DepositadaCompreende uma vacina contendo o antígeno FML (Fucose Mannose-Iigand ou Ligante de Fucose e Manose) e o adjuvante saponina, usada em combinação com quimioterápicos, mostrando propriedade curativa, deixando os cães previamente infectados, na condição de cura estéril da leishmaniose visceral e tegumentar, caracterizada por ausência de parasitas e pela ausência total de DNA de Leishmania, visando impedir a transmissão do parasita causador da Leishmaniose canina visceral do cão para o inseto transmissor e desta forma, para outros cães e humanos. A invenção compreende, também, o uso da citada composição para produzir formulações destinadas a tratar a leishmaniose visceral canina e as leishmanioses viscerais e tegumentares murinas, humanas e caninas, bem como kit compreendendo imunoquimioterápicos para tratar as mesmas patologias

No evidence of association between genetic variants of the PDCD1 ligands and SLE

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldPDCD1, an immunoreceptor involved in peripheral tolerance has previously been shown to be genetically associated with systemic lupus erythematosus (SLE). PDCD1 has two ligands whose genes are located in close proximity on chromosome 9p24. Our attention was drawn to these ligands after finding suggestive linkage to a marker (gata62f03, Z=2.27) located close to their genes in a genome scan of Icelandic families multiplex for SLE. Here, we analyse Swedish trios (N=149) for 23 single nucleotide polymorphisms (SNPs) within the genes of the PDCD1 ligands. Initially, indication of association to eight SNPs was observed, and these SNPs were therefore also analysed in Mexican trios (N=90), as well as independent sets of patients and controls from Sweden (152 patients, 448 controls) and Argentina (288 patients, 288 controls). We do not find support for genetic association to SLE. This is the first genetic study of SLE and the PDCD1 ligands and the lack of association in several cohorts implies that these genes are not major risk factors for SLE.Genes and Immunity (2007) 8, 69-74. doi:10.1038/sj.gene.6364360; published online 30 November 2006

Composição contendo frações de células de Leishmania, denominadas antígeno FML "fucose mannose ligand" ou "ligante de fucose-manose", uso do antígeno FML e de suas subfrações e componentes para as aplicações em imunodiagnóstico específico da leishmaniose visceral humana e animal, para aplicações em vacinação, tratamento ou imunoterapia contra a leishmaniose visceral humana e canina

Em 28/04/1998: Desistência homologada. Notificação da homologação da desistência do pedido de patente, apresentada pelo depositante, acarretando o encerramento do processo administrativo.Não concedidaPatente de invenção: "composições contendo frações nativas de células de Leishmania, denominadas antígeno FML "Ligante de Fucose Manose" e do uso deste antígeno FML e de suas subfrações e componentes: glicoproteínas de 36,55 kd, e outras proteínas, adicionadas ou não de veículos farmacológicos, para as aplicações em imunodiagnóstico específico da leishmaniose visceral humana e animal, e para as aplicações em vacinação, tratamento ou imunoterapia contra a leishmaniose visceral humana e canina