Tularemia Vaccine

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Sergey V Prosorovskii - One of the best experts on this subject based on the ideXlab platform.

  • live Tularemia Vaccine confers protection against lethal legionella and listeria infections in experimental animals
    Fems Immunology and Medical Microbiology, 1996
    Co-Authors: Yuri F Belyi, Igor Tartakovskii, Irina S Mesheryakova, Vladimir V Petrosov, Sergey V Prosorovskii
    Abstract:

    The efficacy of a live Francisella tularensis Vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with Tularemia Vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.

  • research articlelive Tularemia Vaccine confers protection against lethal legionella and listeria infections in experimental animals
    Fems Immunology and Medical Microbiology, 1996
    Co-Authors: Yuri F Belyi, Igor Tartakovskii, Irina S Mesheryakova, Vladimir V Petrosov, Sergey V Prosorovskii
    Abstract:

    The efficacy of a live Francisella tularensis Vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with Tularemia Vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.

Deyu Tian - One of the best experts on this subject based on the ideXlab platform.

  • protective effects of the francisella tularensis δpdpc mutant against its virulent parental strain schu p9 in cynomolgus macaques
    Scientific Reports, 2019
    Co-Authors: Deyu Tian, Akihiko Uda, Yasushi Ami, Akitoyo Hotta, Eunsil Park, Noriyo Nagata, Naoko Iwatayoshikawa, Akio Yamada, Kazuhiro Hirayama
    Abstract:

    Tularemia is a severe infectious zoonotic disease caused by Francisella tularensis. Although F. tularensis is considered to be a potential biological weapon due to its high infectivity and mortality rate, no Vaccine has been currently licensed. Recently, we reported that F. tularensis SCHU P9 derived ΔpdpC strain lacking the pathogenicity determinant protein C gene conferred stable and good protection in a mouse lethal model. In this study, the protective effect of ΔpdpC was evaluated using a monkey lethal model. Two cynomolgus macaques (Macaca fascicularis) intratracheally challenged with the virulent strain SCHU P9 were euthanized on 7 and 11 days post-challenge after the development of severe clinical signs. The bacterial replication in alveolar macrophages and type II epithelial cells in the lungs would cause severe pneumonia accompanied by necrosis. Conversely, two animals subcutaneously immunized with ΔpdpC survived 3 weeks after SCHU P9 challenge. Though one of the two animals developed mild symptoms of Tularemia, bacterial replication was limited in the respiratory organs, which may be due to a high level of humoral and cellular immune responses against F. tularensis. These results suggest that the ΔpdpC mutant would be a safe and promising candidate as a live attenuated Tularemia Vaccine.

  • evaluation of francisella tularensis δpdpc as a candidate live attenuated Vaccine against respiratory challenge by a virulent schu p9 strain of francisella tularensis in a c57bl 6j mouse model
    Microbiology and Immunology, 2018
    Co-Authors: Deyu Tian, Akihiko Uda, Akitoyo Hotta, Eunsil Park, Akio Yamada, Kazuhiro Hirayama, Osamu Fujita, Kozue Hotta, Yuuki Koyama
    Abstract:

    Francisella tularensis, which causes Tularemia, is an intracellular gram-negative bacterium. F. tularensis has received significant attention in recent decades because of its history as a biological weapon. Thus, development of novel Vaccines against Tularemia has been an important goal. The attenuated F. tularensis strain ΔpdpC, in which the pathogenicity determinant protein C gene (pdpC) has been disrupted by TargeTron mutagenesis, was investigated as a potential Vaccine candidate for Tularemia in the present study. C57BL/6J mice immunized s.c. with 1 × 106 CFUs of ΔpdpC were challenged intranasally with 100× the median lethal dose (LD50 ) of a virulent SCHU P9 strain 21 days post immunization. Protection against this challenge was achieved in 38% of immunized C57BL/6J mice administered 100 LD50 of this strain. Conversely, all unimmunized mice succumbed to death 6 days post challenge. Survival rates were significantly higher in vaccinated than in unimmunized mice. In addition, ΔpdpC was passaged serially in mice to confirm its stable attenuation. Low bacterial loads persisted in mouse spleens during the first to tenth passages. No statistically significant changes in the number of CFUs were observed during in vivo passage of ΔpdpC. The inserted intron sequences for disrupting pdpC were completely maintained even after the tenth passage in mice. Considering the stable attenuation and intron sequences, it is suggested that ΔpdpC is a promising Tularemia Vaccine candidate.

Muktha S Natrajan - One of the best experts on this subject based on the ideXlab platform.

  • proteomic analysis of human immune responses to live attenuated Tularemia Vaccine
    Vaccine, 2020
    Co-Authors: Yiehwa Chang, Travis L Jensen, Duc M Duong, Johannes B Goll, David C Wood, Luming Yin, Casey E Gelber, Nicholas T Seyfried, Evan J Anderson, Muktha S Natrajan
    Abstract:

    Francisella tularensis (F. tularensis) is an intracellular pathogen that causes a potentially debilitating febrile illness known as Tularemia. F. tularensis can be spread by aerosol transmission and cause fatal pneumonic Tularemia. If untreated, mortality rates can be as high as 30%. To study the host responses to a live-attenuated Tularemia Vaccine, peripheral blood mononuclear cell (PBMC) samples were assayed from 10 subjects collected pre- and post-vaccination, using both the 2D-DIGE/MALDI-MS/MS and LC-MS/MS approaches. Protein expression related to antigen processing and presentation, inflammation (PPARγ nuclear receptor), phagocytosis, and gram-negative bacterial infection was enriched at Day 7 and/or Day 14. Protein candidates that could be used to predict human immune responses were identified by evaluating the correlation between proteome changes and humoral and cellular immune responses. Consistent with the proteomics data, parallel transcriptomics data showed that MHC class I and class II-related signals important for protein processing and antigen presentation were up-regulated, further confirming the proteomic results. These findings provide new biological insights that can be built upon in future clinical studies, using live attenuated strains as immunogens, including their potential use as surrogates of protection.

  • systems vaccinology for a live attenuated Tularemia Vaccine reveals unique transcriptional signatures that predict humoral and cellular immune responses
    Vaccine, 2019
    Co-Authors: Muktha S Natrajan, Nadine Rouphael, Lilin Lai, Dmitri Kazmin, Travis L Jensen, David Weiss, Chris C Ibegbu, Marcelo B Sztein, William F Hooper
    Abstract:

    Background: Tularemia is a potential biological weapon due to its high infectivity and ease of dissemination. This study aimed to characterize the innate and adaptive responses induced by two different lots of a live attenuated Tularemia Vaccine and compare them to other well-characterized viral Vaccine immune responses. Methods: Microarray analyses were performed on human peripheral blood mononuclear cells (PBMCs) to determine changes in transcriptional activity that correlated with changes detected by cellular phenotyping, cytokine signaling, and serological assays. Transcriptional profiles after Tularemia vaccination were compared with yellow fever [YF-17D], inactivated [TIV], and live attenuated [LAIV] influenza. Results: Tularemia Vaccine lots produced strong innate immune responses by Day 2 after vaccination, with an increase in monocytes, NK cells, and cytokine signaling. T cell responses peaked at Day 14. Changes in gene expression, including upregulation of STAT1, GBP1, and IFIT2, predicted Tularemia-specific antibody responses. Changes in CCL20 expression positively correlated with peak CD8+ T cell responses, but negatively correlated with peak CD4+ T cell activation. Tularemia Vaccines elicited gene expression signatures similar to other replicating Vaccines, inducing early upregulation of interferon-inducible genes. Conclusions: A systems vaccinology approach identified that Tularemia Vaccines induce a strong innate immune response early after vaccination, similar to the response seen after well-studied viral Vaccines, and produce unique transcriptional signatures that are strongly correlated to the induction of T cell and antibody responses.

Vladimir V Petrosov - One of the best experts on this subject based on the ideXlab platform.

  • live Tularemia Vaccine confers protection against lethal legionella and listeria infections in experimental animals
    Fems Immunology and Medical Microbiology, 1996
    Co-Authors: Yuri F Belyi, Igor Tartakovskii, Irina S Mesheryakova, Vladimir V Petrosov, Sergey V Prosorovskii
    Abstract:

    The efficacy of a live Francisella tularensis Vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with Tularemia Vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.

  • research articlelive Tularemia Vaccine confers protection against lethal legionella and listeria infections in experimental animals
    Fems Immunology and Medical Microbiology, 1996
    Co-Authors: Yuri F Belyi, Igor Tartakovskii, Irina S Mesheryakova, Vladimir V Petrosov, Sergey V Prosorovskii
    Abstract:

    The efficacy of a live Francisella tularensis Vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with Tularemia Vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.

  • live Tularemia Vaccine but not proteins purified from francisella tularensis can confer protection against lethal listeria infection in mice
    Apmis, 1995
    Co-Authors: Yura F Belyi, Vladimir V Petrosov, Igor S Tartakovskii, Yuri G Suchkov
    Abstract:

    Immunization of Balb/c mice with Francisella tularensis Vaccine strain 15/10 conferred significant protection against subsequent listerial infection. Since immunostimulatory activities could apparently be relevant to surface components of the bacterium, a technique for purification of cell wall proteins was developed. The scheme designed consisted of Triton X-100 extraction with subsequent FPLC chromatography steps, and resulted in the isolation of homogeneous proteins with molecular masses of 54 kDa (pI = 6.7) and 82 kDa (pI = 5.3), and partially purified 50, 85 and 100 kDa components. It was shown that immunization with isolated proteins failed to protect mice against lethal Listeria monocytogenes infection. Possible reasons for failure are discussed.

Yuri F Belyi - One of the best experts on this subject based on the ideXlab platform.

  • live Tularemia Vaccine confers protection against lethal legionella and listeria infections in experimental animals
    Fems Immunology and Medical Microbiology, 1996
    Co-Authors: Yuri F Belyi, Igor Tartakovskii, Irina S Mesheryakova, Vladimir V Petrosov, Sergey V Prosorovskii
    Abstract:

    The efficacy of a live Francisella tularensis Vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with Tularemia Vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.

  • research articlelive Tularemia Vaccine confers protection against lethal legionella and listeria infections in experimental animals
    Fems Immunology and Medical Microbiology, 1996
    Co-Authors: Yuri F Belyi, Igor Tartakovskii, Irina S Mesheryakova, Vladimir V Petrosov, Sergey V Prosorovskii
    Abstract:

    The efficacy of a live Francisella tularensis Vaccine strain to cause nonspecific immunity toward experimental legionellosis and listeriosis was studied. Immunisation with Tularemia Vaccine protected over 80% and 17% of experimental animals against subsequent lethal challenge with Legionella pneumophila and Listeria monocytogenes, respectively. The protection was maximal during the first month following immunisation and declined thereafter. In order to delineate the immunostimulatory moieties of the Francisella microbe, several cell wall proteins have been purified and characterized. However, isolated cell wall components failed to induce protection.