Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease.

Blander, S J; Horwitz, Marcus A.

doi:10.1172/jci116253

Cited by 75 publications

(43 citation statements)

References 38 publications

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“…These complexes serve to alert the host immune system to the presence of a pathogen sequestered within the host cell, allowing it to mount an appropriate antimicrobial response. As in previous studies (3)(4)(5), in which immunization with either of two major extracellular proteins of Legionella pneumophila, the agent of Legionnaires' disease, was demonstrated to enhance the survival of guinea pigs after challenge by aerosol with L. pneumophila, this study shows that immunization with a major extracellular protein of M. tuberculosis, albeit via a live vector rather than as a protein in an adjuvant, enhances survival after challenge by aerosol with M. tuberculosis in a highly susceptible animal model.…”

Section: Vol 71 2003 a New Tb Vaccine Enhances Survival After Challmentioning

confidence: 57%

A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis

2003

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Tuberculosis (TB) remains an enormous global health problem, and a new vaccine against TB more potent than the current inadequate vaccine, Mycobacterium bovis BCG, is urgently needed. We describe a recombinant BCG vaccine (rBCG30) expressing and secreting the 30-kDa major secretory protein of Mycobacterium tuberculosis, the primary causative agent of TB, that affords greater survival after challenge than parental BCG in the highly demanding guinea pig model of pulmonary TB. Animals immunized with rBCG30 and then challenged by aerosol with a highly virulent strain of M. tuberculosis survived significantly longer than animals immunized with conventional BCG. The parental and recombinant vaccine strains are comparably avirulent in guinea pigs, as they display a similar pattern of growth and clearance in the lung, spleen, and regional lymph nodes. The pMTB30 plasmid encoding the 30-kDa protein is neither self-transmissible nor mobilizable to other bacteria, including mycobacteria. The pMTB30 plasmid can be stably maintained in Escherichia coli but is expressed only in mycobacteria. The recombinant and parental strains are sensitive to the same antimycobacterial antibiotics. rBCG30, the first vaccine against TB more potent than nearly century-old BCG, is being readied for human clinical trials.Tuberculosis continues as a major global health problem, especially in the developing world where 1 in 6 adults between the ages of 15 and 59 dies from this disease (10, 22). The AIDS epidemic, whose victims are severalfold more susceptible to tuberculosis than the general population, and the worldwide emergence of drug-resistant strains of Mycobacterium tuberculosis, the primary causative agent of tuberculosis, compound the problem (8,14). A better vaccine against tuberculosis is urgently needed (11, 23). The current vaccine, Mycobacterium bovis BCG, a live attenuated vaccine derived from the bovine tuberculosis bacillus in the early 1900s by Calmette and Guérin, while protective against disseminated forms of tuberculosis such as meningitis and miliary tuberculosis, is of inconsistent efficacy against pulmonary tuberculosis, the dominant form (9, 12).In a previous study (20), two recombinant BCG vaccines (rBCG30) overexpressing the major secretory protein of M. tuberculosis, a 30-kDa mycolyl transferase (2, 27), were described. This protein is not only the major secretory protein of M. tuberculosis in broth culture (19) but it is also among the major proteins of all M. tuberculosis proteins expressed in human macrophages (15, 21). Derived from the commercially available Connaught (Conn) and Tice strains of BCG, the recombinant vaccines were tested in the demanding guinea pig model of pulmonary tuberculosis. In contrast to other small animals used for models of tuberculosis, guinea pigs are much more susceptible to tuberculosis than humans, yet they develop disease that closely mimics human disease clinically, immunologically, and pathologically. Guinea pigs immunized with the recombinant vaccines and then challenged by aerosol...

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Section: Vol 71 2003 a New Tb Vaccine Enhances Survival After Challmentioning

confidence: 57%

A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis

2003

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“…It has been confirmed that immunisation with homologous Hsp60 protects laboratory animals against experimental challenge with Salmonella enteric serovar Typhi (Paliwal et al 2008;Bansal et al 2010), Helicobacter pylori (Yamaguchi et al 2000;Yamaguchi et al 2003), Histoplasma capsulatum (Gomez et al 1995;Deepe and Gibbons 2002), Legionella pneumophila (Blander and Horwitz 1993;Weeratna et al 1994), Yersinia enterocolitica (Noll and Autenrieth 1996), Chlamydia trachomatis (Rank et al 1995), Paracoccidioides brasiliensis (Soares et al 2008), Piscirickettsia salmonis (Wilhelm et al 2005) and Francisella tularensis (Hartley et al 2004). Because of the broad cross-reactivity of H. somni Hsp60 antibodies (Galli 2009;Bajzert 2013) with Hsp60 of Pasteurella multocida, Escherichia coli and Salmonella Enteritidis, it seems to be an promising candidate to vaccinate farm animals and to induce cross-protection.…”

Section: Discussionmentioning

confidence: 96%

Humoral and cellular immune response to Histophilus somni recombinant heat shock protein 60 kDa in farm animals

Jankowska¹,

Bajzert²,

Pisarek³

et al. 2015

Vet. Med.

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ABSTRACT:The aim of this study was to evaluate the effects of immunising farm animals with the Histophilus somni recombinant heat shock protein 60kDa (H. somni rHsp60) in field conditions. Fifty piglets, 10 calves and 30 hens were immunised twice, and the same number of each species was used as the control. The humoral immune response was evaluated using ELISA in piglets (IgG, IgA and IgM) and calves (IgG 1 , IgG 2 and IgM) sera and in hen egg yolks (IgY). Cell-mediated immune responses were evaluated using the skin test. Concentrations of serum haptoglobin in calves and piglets and plasma fibrinogen in calves, daily weight gain in piglets, as well as the inner body temperature and clinical signs in calves were measured to evaluate the clinical effects of vaccination. In animals immunised twice with H. somni rHsp60, a statistically significant increase in IgY antibodies in egg yolk as well as serum IgG 1 and IgG 2 antibodies in calves (P < 0.05) was found. In piglets, the antibody reaction against H. somni rHsp60 was higher in the experimental than in the control group, but the difference was significant only for the IgG class (P < 0.05). A moderate cell-mediated immune response to H. somni rHsp60 measured using the skin test was observed in piglets after 24 h (P < 0.05), but not in calves and hens. The daily weight gain was significantly higher in the experimental than in the control piglets (P < 0.05). The fibrinogen and haptoglobin levels in calves, as well as the inner body temperature, indicated a reduced risk of pathology in the experimental group of calves. The preliminary results confirmed the immunogenicity of H. somni rHsp60. A beneficial effect on piglet weight gain was observed. The obtained results warrant further studies of the protective effects of H. somni rHsp60 as an ingredient of subunit vaccines in farm animals.

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“…Few animals immunized with the low dose (10 1 CFU) developed antibody titers above background and even then the titers were modest. In contrast, animals immunized with the high dose (1,2,(23)(24)(25)(26). In this regard, the 30 kDa protein is the major protein secreted by M. tuberculosis in broth culture (24) and among the most abundantly expressed proteins of all types produced by M. tuberculosis within human macrophages (27).…”

Section: Discussionmentioning

confidence: 99%

Extraordinarily few organisms of a live recombinant BCG vaccine against tuberculosis induce maximal cell-mediated and protective immunity

Horwitz

Harth

Dillon

et al. 2006

Vaccine

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Major cytoplasmic membrane protein of Legionella pneumophila, a genus common antigen and member of the hsp 60 family of heat shock proteins, induces protective immunity in a guinea pig model of Legionnaires' disease.

Cited by 75 publications

References 38 publications

A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis

A New Vaccine against Tuberculosis Affords Greater Survival after Challenge than the Current Vaccine in the Guinea Pig Model of Pulmonary Tuberculosis

Humoral and cellular immune response to Histophilus somni recombinant heat shock protein 60 kDa in farm animals

Extraordinarily few organisms of a live recombinant BCG vaccine against tuberculosis induce maximal cell-mediated and protective immunity

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