35 research outputs found
Identification of Continuous Human B-Cell Epitopes in the Envelope Glycoprotein of Dengue Virus Type 3 (DENV-3)
BACKGROUND:Dengue virus infection is a growing global public health concern in tropical and subtropical regions of the world. Dengue vaccine development has been hampered by concerns that cross-reactive immunological memory elicited by a candidate vaccine could increase the risk of development of more severe clinical forms. One possible strategy to reduce risks associated with a dengue vaccine is the development of a vaccine composed of selected critical epitopes of each of the serotypes. METHODOLOGY/PRINCIPAL FINDINGS:Synthetic peptides were used to identify B-cell epitopes in the envelope (E) glycoprotein of dengue virus type 3 (DENV-3). Eleven linear, immunodominant epitopes distributed in five regions at amino acid (aa) positions: 51-65, 71-90, 131-170, 196-210 and 246-260 were identified by employing an enzyme- linked immunosorbent assay (ELISA), using a pool of human sera from dengue type 3 infected individuals. Peptides 11 (aa51-65), 27 and 28 (aa131-150) also reacted with dengue 1 (DENV-1) and dengue 2 (DENV-2) patient sera as analyzed through the ROC curves generated for each peptide by ELISA and might have serotype specific diagnostic potential. Mice immunized against each one of the five immunogenic regions showed epitopes 51-65, 131-170, 196-210 and 246-260 elicited the highest antibody response and epitopes131-170, 196-210 and 246-260, elicited IFN-gamma production and T CD4+ cell response, as evaluated by ELISA and ELISPOT assays respectively. CONCLUSIONS/SIGNIFICANCE:Our study identified several useful immunodominant IgG-specific epitopes on the envelope of DENV-3. They are important tools for understanding the mechanisms involved in antibody dependent enhancement and immunity. If proven protective and safe, in conjunction with others well-documented epitopes, they might be included into a candidate epitope-based vaccine
Gene Expression Profiling during Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome
Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. © 2009 Nascimento et al
Efeitos de imunopotenciadores nĂŁo especĂficos na infecção experimental pelo Schistosoma mansoni: I. levamisole
The effects of levamisole on the histopathological changes, host's resistance and "in vivo" chemotaxis in Schistosoma mansoni experimental infection of C57B1/10 inbred mice were studied. Prophylatic treatment resulted in an increase in the number of adult worms obtained by perfusion and also increased the mortality rate (p < 0.05). The histopathological changes (liver and intestines) were similar in all the groups. A significant reduction of "in vivo" chemotaxis occurred in infected control mice as well as in those submitted to prophylatic treatment with levamisole. Chemotatic activity reached the same levels of normal control mice (non-infected and non-treated with levamisole), when the curative scheme was used. Levamisole seems to increase the susceptibility of inbred C57B1/10 mice to the infection with S. mansoni when administered prior to the infection and increase the chemotatic activity to normal levels when given after infection.Os efeitos do levamisole nas alterações histopatolĂłgicas, resistĂŞncia do hospedeiro e quimiotaxia "in vivo" foram estudados na infecção experimental pelo Schistosoma mansoni em camundongos da linhagem C57B1/10. O tratamento profilático resultou em um aumento no nĂşmero de vermes adultos obtidos pela perfusĂŁo e tambĂ©m em uma taxa de mortalidade maior (p < 0,05). As alterações histopatolĂłgicas (fĂgado e intestino) foram similares em todos os grupos. Uma redução significante da quimiotaxia "in vivo" ocorreu em camundongos controles infectados, assim como naqueles submetidos a tratamento profilático com levamisole. A atividade quimiotática atingiu os mesmos nĂveis dos camundongos controles normais (nĂŁo-infectados e nĂŁo-tratados com levamisole), quando o esquema curativo foi usado. O levamisole parece aumentar a susceptibilidade de camundongos da linhagem C57B1/10 Ă infecção pelo S. mansoni quando administrado antes da infecção e normaliza a atividade quimiotática, quando dado apĂłs a infecção
Liver and serum soluble protein changes and pathomorphology in undernourished mice with acute Schistosomiasis mansoni
Body, liver and spleen weights; histopathology of the liver, spleen and intestines; hepatic and serum soluble proteins changes were the parameters studied in undernourished Swiss albino mice experimentally infected with S. mansoni. Non-infected deficient animab had lower liver/body weight and spleen/body weight ratios as compared to the controls (22.60% casein group). Infected mice showed higher values regardless the type of diet. Undernourished infected subgroup showed a persistent exudative periovular reaction in the liver. Soluble hepatic proteins content and serum protein fractions appeared to be lower in the deficient infected mice. A significant difference was detected in the gammaglobulin fraction between infected and non-infected animals fed the control diet with higher values for the former. Our data suggest that the effects of malnutrition, per se, are sometimes more detrimental to the host than those due to Manson 's schistosomiasis.<br>No presente estudo os pesos corporal, hepático e esplĂ©nico; a morfologia patolĂłgica do fĂgado, baço e intestinos; e as modificações das proteĂnas solĂşveis hepáticas e sĂ©ricas, foram os parâmetros investigados em camundongos albinos SuĂços desnutridos e infectados com S. mansoni. Os animais desnutridos nĂŁo infectados apresentaram relações fĂgado/peso corporal e baço! peso corporal com valores menores do que os animais controles (grupo caseina a 22,60%). Camundongos infectados mostraram esses Ăndices mais elevados, independentemente do tipo de dieta. O subgrupo de camundongos desnutridos infectados apresentou, no fĂgado, reação periovular exsudativa persistente. O conteĂşdo de proteĂnas solĂşveis no fĂgado e no soro tambĂ©m mostrou-se reduzido nos camundongos infectados desnutridos. Diferença significativa foi detectada quanto Ă s gamaglobulinas, comparando-se animais infectados com nĂŁo infectados alimentados com a dieta controle II, valores mais altos ocorrendo no grupo dos infectados. Especula-se que os efeitos da má nutrição podem ser mais prejudiciais ao hospedeiro do que aqueles provocados pelo S. mansoni