12 research outputs found

    Parameters of the attenuated schistosome vaccine evaluated in the olive baboon

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    Five exposures of baboons to the attenuated schistosome vaccine gave greater protection than three exposures, but this attenuation was not sustained when challenge was delayed. Within the scope of the data collected, fecal egg counts and circulating antigen levels did not accurately predict the observed worm burdens. Levels of immunoglobulin G at challenge correlated best with protection, but there was little evidence of a recall response

    The Parasite specifity of cytotoxic T cells from cattle immunized with Buffalo and cattle- derived Theileria parva parasites.

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    Immunity to East Coast fever, a parasitic disease of cattle, is partially attributable to a cell-mediated immune response directed at cells infected with the schizont stage of the parasite. This response is in the form of cytotoxic T cells which can be measured in vitro after stimulating peripheral blood mononuclear cells (PBM) from immune animals (but not from naive animals) with their own autologous Theileria parva~infected cells. This study evaluated the parasite strain specificity of cytotoxic cells generated in cattle immunized with one of 5 different stocks of buffalo-derived T.parva lawrencei parasites or with cattle-derived T.p.parva (Uganda) or T.p.bovis (Boleni) parasite stocks. The objective was to determine whether any of these stocks was able to generate non-strain restricted immune T cells, that would recognize and subsequently lyse lymphocytes infected with different strains of T.parva parasites. Ultimately such information would be useful in identifying an antigen on the surface of schizont-infected cells which is common among cell lines infected with many different strains or stocks of T.parva parasites, and which could potentially form the basis of a recombinant subunit vaccine against East coast fever. To do this a group of 7 embryo transfer cattle, sharing the same parents and matched for at least one bovine lymphocyte antigen (BoLA) A-locus specificity, were immunized by infection and treatment. Cell lines to be used as target cells in in vitro cytotoxicity assays were generated by infection of PBM with the 5 buffalo parasite stocks as well as with the cattle-derived parasite stocks T.p.parva (Uganda), (Muguga), (Marikebuni), (Mariakani), and T.p.bovis (Boleni). PBM from the 7 cattle were evaluated in cytotoxicity assays following repeated stimulation in vitro with autologous or major histocompatibility complex (MHC)-matched cells infected with the same parasite stock as was used for immunization of the animal. It was possible to generate cytotoxic cells from all 7 cattle which were specific for MHC-matched cells infected with T.parva parasites. Testing for MHC restriction specificity using a panel of lymphocytes of different MHC backgrounds but infected with a single T.parva parasite stock were carried out and the results indicated bias in response towards one of the 2 BoLA A-locus class 1 specificities of the donor animals. In addition, limiting dilution assays for the estimation of the frequency of precursors of cytotoxic T cells with various parasite specificities in the blood of the immune cattle were carried out for 5 of the animals. The results in terms of parasite specificity of cytotoxic cells were very similar to those obtained with in vitro cytotoxicity assays. In summary, these experiments have revealed that the buffalo-derived parasite stocks Tp1(7014), (7013), (6999), (7065), (6998) and the cattle derived Ipp(Uganda) stock were able to induce generation of cytotoxic I-cells in vivo which are capable of recognizing parasite antigens on cells infected with many different T.parva parasite stocks although the proportion of cells killed was low for some of the cell lines. Further, lymphocytes from 1 steer which had cytolytic activity against a large number of infected cell lines were cloned in order to determine- if individual immune I-cells were recognizing antigenic epitope(s) common among cells infected with different stocks of I.parva, or if the broad specificity of killing was due to a heterologous mix of cytotoxic cells with varying antigen specificities. Two of the I cell cytotoxic clones generated gave greater than 50% cytotoxicity on all of the infected target cells at an effector to target ratio of less than 5:1. Such cloned cells will be very useful in future studies designed to identify the common or cross-reactive antigenic epitope and the parasite gene encoding for it, with a view towards constructing a recombinant vaccine against East coast fever

    Immunization with Theileria parva parasites from buffaloes results in generation of cytotoxic T cells which recognize antigens common among cells infected with stocks of T. parva parva, T. parva bovis, and T. parva lawrencei

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    Immunity to infection by the protozoan parasite Theileria parva in cattle is partially attributable to cytotoxic T cells, which kill lymphocytes infected with the schizont stage of the parasite. Here we evaluated five stocks of buffalo-derived T. parva lawrencei parasites and two stocks of cattle-derived T. parva parasites for their ability to induce in vivo cytotoxic T cells which can kill lymphocytes infected with a wide variety of strains of T. parva parasites. A group of seven full-sibling cattle, produced by embryo transfer and matched for at least one major histocompatibility complex class I haplotype, were immunized by infection and treatment with the parasite stocks. Target cells used in vitro cytotoxicity assays were infected with five buffalo-derived parasite stocks and five cattle-derived parasite stocks, including T. parva and T. parva bovis. Immunization with any of the seven parasite stocks resulted in the generation of cytotoxic T cells which recognized parasite antigens on most if not all of the target cell lines tested, although the T. parva bovis stock was the least effective at doing so. Further in-depth analyses performed with peripheral blood mononuclear cells from one of the cattle immunized with T. parva lawrencei parasites showed that the pattern of killing of the panel of target cells was altered when either cells infected with different parasite stocks or clones of infected cells were used as stimulator cells in vitro, suggesting the presence of more than one population of parasite-specific cytotoxic effector cells in the peripheral blood mononuclear cells. However, clones of these cytotoxic effector cells recognized common or cross-reactive antigen epitopes expressed by the entire panel of infected target cells. These T-cell clones will be useful for identifying common T-cell antigen epitopes of T. parva and the parasite genes encoding them

    Immunity against HIV/AIDS, Malaria, and Tuberculosis during Co-Infections with Neglected Infectious Diseases: Recommendations for the European Union Research Priorities.

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    Contains fulltext : 69872.pdf (publisher's version ) (Open Access)Author SummaryInfectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective

    Immunity against HIV/AIDS, malaria, and tuberculosis during co-infections with neglected infectious diseases: recommendations for the European Union research priorities

    No full text
    Infectious diseases remain a major health and socioeconomic problem in many low-income countries, particularly in sub-Saharan Africa. For many years, the three most devastating diseases, HIV/AIDS, malaria, and tuberculosis (TB) have received most of the world's attention. However, in rural and impoverished urban areas, a number of infectious diseases remain neglected and cause massive suffering. It has been calculated that a group of 13 neglected infectious diseases affects over one billion people, corresponding to a sixth of the world's population. These diseases include infections with different types of worms and parasites, cholera, and sleeping sickness, and can cause significant mortality and severe disabilities in low-income countries. For most of these diseases, vaccines are either not available, poorly effective, or too expensive. Moreover, these neglected diseases often occur in individuals who are also affected by HIV/AIDS, malaria, or TB, making the problem even more serious and indicating that co-infections are the rule rather than the exception in many geographical areas. To address the importance of combating co-infections, scientists from 14 different countries in Africa and Europe met in Addis Ababa, Ethiopia, on September 9-11, 2007. The message coming from these scientists is that the only possibility for winning the fight against infections in low-income countries is by studying, in the most global way possible, the complex interaction between different infections and conditions of malnourishment. The new scientific and technical tools of the post-genomic era can allow us to reach this goal. However, a concomitant effort in improving education and social conditions will be needed to make the scientific findings effective
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