Does Immunotherapy Protect Equines from Reinfection by the Oomycete Pythium insidiosum?

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Immunotherapy against experimental canine visceral leishmaniasis with the saponin enriched-Leishmune((R)) vaccine

In order to assess the immunotherapeutic potential on canine visceral leishmaniasis of the Leishmune (R) vaccine, formulated with an increased adjuvant concentration (1 mg of saponin rather than 0.5 mg), 24 mongrel dogs were infected with Leishmania (L.) chagasi. The enriched-Leishmune (R) vaccine was injected on month 6, 7 and 8 after infection, when animals were seropositive and symptomatic. The control group were injected with a saline solution. Leishmune (R)-treated dogs showed significantly higher levels of anti-FML IgG antibodies (ANOVA; p < 0.0001), a higher and stable IgG2 and a decreasing IgG I response, pointing to a TH1 T cell mediated response. The vaccine had the following effects: it led to more positive delayed type hypersensitivity reactions against Leishmania lysate in vaccinated dogs (75%) than in controls (50%), to a decreased average of CD4+ Leishmania-specific lymphocytes in saline controls (32.13%) that fell outside the 95% confidence interval of the vaccinees (41.62%, CI95% 43.93-49.80) and an increased average of the clinical scores from the saline controls (17.83) that falls outside the 95% confidence interval for the Leishmune (R) immumotherapy-treated dogs (15.75, CI95% 13.97-17.53). All dogs that received the vaccine were clustered, and showed lower clinical scores and normal CD4+ counts, whereas 42% of the untreated dogs showed very diminished CD4+ and higher clinical score. The increase in clinical signs of the saline treated group was correlated with an increase in anti-FML antibodies (p < 0.0001), the parasitological evidence (p = 0.038) and a decrease in Leishinania-specific CD4+ lymphocyte proportions (p = 0.035). These results confirm the immunotherapeutic potential of the enriched-Leishmune (R) vaccine. The vaccine reduced the clinical symptoms and evidence of parasite, modulating the outcome of the infection and the dog's potential infectiosity to phlebotomines. The enriched-Leishmune (R) vaccine was subjected to a safety analysis and found to be well tolerated and safe. (c) 2007 Elsevier Ltd. All rights reserved.

Immunotherapy with the saponin enriched-Leishmune (R) vaccine versus immunochemotherapy in dogs with natural canine visceral leishmaniasis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Is the BCG Vaccine Safe for Undernourished Individuals?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Neonatal BCG Immunization Followed by DNAhsp65 Boosters: Highly Immunogenic but not Protective Against Tuberculosis - a Paradoxical Effect of the Vector?

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Saponins, IL12 and BCG adjuvant in the FML-vaccine formulation against murine visceral leishmaniasis

The FML antigen of Leishmania donovani, in combination with either Riedel de Haen (R), QuilA, QS21 saponins, IL12 or BCG, was used in vaccination of an outbred murine model against visceral leishmaniasis (VL). Significant and specific increases in anti-FML IgG and IgM responses were detected for all adjuvants, and in anti-FML IgG1, IgG2a and IgG2b and delayed type of hypersensitivity to L. donovani lysate (DTH), only for all saponins and IL12. The QS21-FML and QuilA-FML groups achieved the highest IgG2a response. QuilA-FML developed the strongest DTH and QS21-FML animals showed the highest serum IFN-gamma concentrations. The reduction of parasitic load in the liver in response to each FML-vaccine formulation was: 52% (P < 0.025) for BCG-FML, 73% (P < 0.005) for R-FML, 93% (P < 0.005) for QuilA-FML and 79.2% (P < 0.025) for QS21-FML treated animals, respectively. Protection was specific for R-FML and QS21-FML while the QuilA saponin treatment itself induced 69% of LDU reduction. The FML-saponin vaccines promote significant, specific and strong protective effects against murine visceral leishmaniasis. BCG-FML induced minor and non-specific protection while IL 12-FML, although enhancing the specific antibody and IDR response, failed to reduce the parasitic load of infected animals. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

Immunotherapy against murine experimental visceral leishmaniasis with the FML-vaccine

The fucose mannose ligand (Leishmania donovani FML)-saponin vaccine has earlier shown its immunoprophylactic potential against visceral leishmaniasis in the CB hamster (87.7% of parasite load reduction), Balb/c (84.4%) and Swiss albino mouse (85-93%) models. In this investigation its specific immunotherapeutic efficacy against L. donovani infection in Balb/c mice was studied. The effects of vaccine treatment on the Immoral response, delayed type of hypersensitivity to promastigote lysate (DTH), cytokine levels in sera and reduction of the liver parasitic load of L. donovani infected mice, were examined. The types and subtypes of anti-FML antibodies increased significantly in the vaccinees over the saline and saponin controls. As expected for a saponin vaccine, the highest ratios were found in relation to IgG1, IgG2a and IgG2b (4.4, 5 and 2.5, respectively). The DTH response and the in vitro ganglion cell proliferative response against FML antigen were also significantly higher than controls (P < 0.005). Concomitantly, an impressive and specific decrease of liver parasitic burden was detected only in vaccine-treated animals (94.7%). Our results indicate that the therapeutic FML-vaccine has a potent effect on modulation of the murine infection leading to the reduction of parasitic load and signs of disease, being a new potential tool in the therapy and control of visceral leishmaniasis. (C) 2003 Elsevier Ltd. All rights reserved.

AVALIACAO DA REACAO DE MITSUDA EM PACIENTES VIRCHOVIANOS INATIVOS ANTES E APOS IMUNOTERAPIA

In this study the immunopotentiator levamisole as well as a mixture of BCG/Mycobacterium leprae were investigated in inactive lepromatous leprosy patients by using the Mitsuda reaction as a parameter. Twenty lepromatous patients ten years ago classified as histologically negative for Mitsuda's test were divided into three groups: five patients that were only retested with Mitsuda antigen; eight patients that received oral levamisol and seven patients that received a mixture of alive BCG plus autoclaved M. leprae. The results indicated that: 1) the levamisole did not alter the reactivity to lepromin in any of the patients studied; 2) neither the changes in the reactivity to lepromin by using the mixture (3 cases) nor those that occurred spontaneously (3 cases) were clear. They properly reflected the natural variation of patients with some degree of resistance to Mycobacterium leprae.

Immunomodulatory effects of low dose chemotherapy and perspectives of its combination with immunotherapy

Given that cancer is one of the main causes of death worldwide, many efforts have been directed toward discovering new treatments and approaches to cure or control this group of diseases. Chemotherapy is the main treatment for cancer; however, a conventional schedule based on maximum tolerated dose (MTD) shows several side effects and frequently allows the development of drug resistance. On the other side, low dose chemotherapy involves antiangiogenic and immunomodulatory processes that help host to fight against tumor cells, with lower grade of side effects. In this review, we present evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics, can be better than or as efficient as MTD. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provides us with sufficient evidence that low concentrations of selected chemotherapeutic agents, rather than conventional high doses, should be evaluated in combination with immunotherapy. Copyright © 2012 UICC.

Efeito da desnutrição experimental na resposta imune induzida por BCG e DNAhsp65

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

BCG and BCG/DNAhsp65 Vaccinations Promote Protective Effects without Deleterious Consequences for Experimental Autoimmune Encephalomyelitis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Response of splenic melanomacrophage centers of Oreochromis niloticus (Linnaeus, 1758) to inflammatory stimuli by BCG and foreign bodies

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeito modulador da estratégia vacinal BCG/DNAhsp65 na encefalite autoimune experimental(EAE)

Tanto o BCG (Bacilo de Calmette-Guérin) quanto a DNAhsp65 são vacinas contra tuberculose, porém além da atividade protetora desejável ambas apresentam atividade imunomoduladora. Seguindo a linha de pesquisa de nosso laboratório que investiga a atividade da DNAhsp65 sobre doenças autoimunes, avaliamos o efeito da associação destas vacinas sob a forma de uma estratégia vacinal tipo prime-boost (priming com BCG seguida de booster com DNAhsp65), sobre o desenvolvimento da Encefalite Autoimune Experimental (EAE), que é modelo animal de esclerose múltipla. Ratos Lewis fêmeas foram divididos em grupos de 5 a 6 animais (salina, BCG, EAE, BCG/EAE, BCG/vetor/EAE e BCG/vacina/EAE) e imunizados em intervalos de 15 dias. Os animais receberam um primming com 2 - 10 x 105 unidades formadoras de colônias de BCG subcutâneo seguido de dois boosters com 300 g de pVAXhsp65 numa solução de sacarose 25% por via intramuscular. A EAE foi induzida 15 dias após a última imunização, por inoculação de 25 g de proteína básica de mielina (MBP) associada ao Adjuvante Completo de Freund contendo Mycobacterium butyricum. Aqueles que não receberam os inóculos descritos foram injetados com salina, exceto o grupo BCG/vetor/EAE que recebeu 300 g de pVAX (vetor plasmidial vazio) também em solução de sacarose. Os animais foram acompanhados diariamente até serem submetidos à eutanásia, 3 semanas mais tarde, durante a fase de recuperação da doença para avaliação da resposta imune, escore clínico e presença de infiltrado inflamatório no SNC. A evolução clínica da EAE foi similar entre animais vacinados e não vacinados, mas a análise histopatológica revelou que a imunização prévia com BCG ou BCG/DNAhsp65 diminui o processo inflamatório. No cérebro foi observada redução acentuada do processo inflamatório nos grupos BCG/EAE, ...(Resumo completo, clicar acesso eletrônico abaixo)

Immunomodulatory effects of low dose chemotherapy and perspectives of combanation with immunotherapy

Nowadays cancer is one of the main causes of death and many efforts worldwide have been driven to find out new treatments and approaches in order to extinguish or reduce this group of disorder. Chemotherapy is the main treatment for cancer, however, conventional schedule based on maximum tolerated dose (MTD) show several side effects and frequently allow the development of drug resistance. In this review we present the evidence that metronomic chemotherapy, based on the frequent administration of low or intermediate doses of chemotherapeutics is as efficient as MTD and works better in some situations. Finally, we present some data indicating that noncytotoxic concentrations of antineoplastic agents are able to both up-regulate the immune system and increase the susceptibility of tumor cells to cytotoxic T lymphocytes. Taken together, data from the literature provide us the evidence that low concentrations of selected chemotherapeutics agents, rather than conventional high doses, should be chosen for combination with immunotherapy