scholarly journals Assessment ofMycobacterium bovisDeleted inp27-p55Virulence Operon as Candidate Vaccine against Tuberculosis in Animal Models

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
María V. Bianco ◽  
Simon Clark ◽  
Federico C. Blanco ◽  
Sergio Garbaccio ◽  
Elizabeth García ◽  
...  
Keyword(s):  
Animal Models ◽  
Mycobacterium Bovis ◽  
Nude Mice ◽  
Parental Strain ◽  
Guinea Pigs ◽  
Candidate Vaccine ◽  
Th1 Response

AMycobacterium bovisknockout inp27-p55operon was tested as an antituberculosis experimental vaccine in animal models. The mutant MbΔp27-p55 was significantly more attenuated in nude mice than its parental strain but more virulent than BCG Pasteur. Challenge experiments in mice and guinea pigs usingM. bovisorM. tuberculosisstrains showed similar protection conferred by MbΔp27-p55 mutant than BCG in terms of pathology and bacterial loads in spleen but lower protection than BCG in lungs. When tested in cattle, MbΔp27-p55 did not induce IL-2 expression and induced a very low production of IFNγ, suggesting that the lack of P27/P55 reduces the capacity ofM. bovisof triggering an adequate Th1 response.

In-vitro and in-vivo Evaluation of Anti-asthmatic Activity of Eugenia jambolana bark

2021 ◽  
pp. 3337-3342
Author(s):  
Bhong Prabha N. ◽  
Naikawade Nilofar. S. ◽  
Mali Pratibha. R. ◽  
Bindu Madhavi. S.
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Animal Models ◽  
Aqueous Extract ◽  
Guinea Pigs ◽  
Bark Extract ◽  
Eugenia Jambolana ◽  
In Vivo Animal Models

Objectives: The present study designed to evaluate the Antiasthmatic activity of aqueous extract of bark of Eugenia Jambolana (AEEJ) on in vitro and in vivo animal models. Materials and methods: Different in vitro and in vivo animal models was used to study the anti asthmatic activity as isolated goat tracheal chain preparation, Acetylcholine and Histamine induced bronconstriction in guinea pigs, effect of drug extract on histamine release from mast cell was checked by clonidine-induced mast cell degranulation, and milk-induced eosinophilia and leukocytosis. Results: In-vitro study on goat tracheal chain preparation revealed that aqueous extract of Eugenia jambolana (AEEJ)bark exerted antagonistic effect on the histamine induced contraction. (P<0.05) The guinea pigs when exposed to 0.2% histamine aerosol showed signs of progressive dyspnoea leading to convulsions. AEEJ significantly prolonged the latent period of convulsions (PCT) as compared to control following the exposure of histamine (0.2%) aerosol (P<0.01). The observation of present study indicates aqueous extract of Eugenia jambolana shows significant inhibition of milk induced eosinophilia and leukocytosis. Group of animals pretreated with aqueous Eugenia jambolana bark extract showed significant reduction in degranulation of mast cells when challenged with clonidine. The prevention of degranulation process by the aqueous Eugenia jambolana bark extract (P<0.01) indicates a possible stabilizing effect on the mast cells, indicating mast cell stabilizing activity. Conclusions: Thus, AEEJ showed antihistaminic, mast cell stabilizing and protective in guinea pigs against histamine induced PCD, reduced eosinophilia and leukocytosis and hence possesses potential role in the treatment of asthma.

scholarly journals Differential Contribution of Bacillus anthracis Toxins to Pathogenicity in Two Animal Models

2012 ◽  
Vol 80 (8) ◽  
pp. 2623-2631 ◽  
Author(s):  
Haim Levy ◽  
Shay Weiss ◽  
Zeev Altboum ◽  
Josef Schlomovitz ◽  
Itai Glinert ◽  
...  
Keyword(s):  
Animal Models ◽  
Guinea Pigs ◽  
Protective Antigen ◽  
Comprehensive Evaluation ◽  
Lethal Factor ◽  
Rabbit Model ◽  
Content Type ◽  
Edema Factor ◽  
Genes Encoding ◽  
Guinea Pig Model

ABSTRACTThe virulence ofBacillus anthracis, the causative agent of anthrax, stems from its antiphagocytic capsule, encoded by pXO2, and the tripartite toxins encoded by pXO1. The accepted paradigm states that anthrax is both an invasive and toxinogenic disease and that the toxins play major roles in pathogenicity. We tested this assumption by a systematic study of mutants with combined deletions of thepag,lef, andcyagenes, encoding protective antigen (PA), lethal factor (LF), and edema factor (EF), respectively. The resulting seven mutants (single, double, and triple) were evaluated following subcutaneous (s.c.) and intranasal (i.n.) inoculation in rabbits and guinea pigs. In the rabbit model, virulence is completely dependent on the presence of PA. Any mutant bearing apagdeletion behaved like a pXO1-cured mutant, exhibiting complete loss of virulence with attenuation indices of over 2,500,000 or 1,250 in the s.c. or i.n. route of infection, respectively. In marked contrast, in guinea pigs, deletion ofpagor even of all three toxin components resulted in relatively moderate attenuation, whereas the pXO1-cured bacteria showed complete attenuation. The results indicate that a pXO1-encoded factor(s), other than the toxins, has a major contribution to the virulence mechanism ofB. anthracisin the guinea pig model. These unexpected toxin-dependent and toxin-independent manifestations of pathogenicity in different animal models emphasize the importance and need for a comprehensive evaluation ofB. anthracisvirulence in general and in particular for the design of relevant next-generation anthrax vaccines.

scholarly journals Coxiella burnetii Intratracheal Aerosol Infection Model in Mice, Guinea Pigs, and Nonhuman Primates

2019 ◽  
Vol 87 (12) ◽  
Author(s):  
A. E. Gregory ◽  
E. J. van Schaik ◽  
K. E. Russell-Lodrigue ◽  
A. P. Fratzke ◽  
J. E. Samuel
Keyword(s):  
Animal Models ◽  
Coxiella Burnetii ◽  
Guinea Pigs ◽  
Nonhuman Primates ◽  
Q Fever ◽  
Febrile Illness ◽  
Cell Vaccine ◽  
Infection Model ◽  
Atypical Pneumonia ◽  
Content Type

ABSTRACT Coxiella burnetii, the etiological agent of Q fever, is a Gram-negative bacterium transmitted to humans by inhalation of contaminated aerosols. Acute Q fever is often self-limiting, presenting as a febrile illness that can result in atypical pneumonia. In some cases, Q fever becomes chronic, leading to endocarditis that can be life threatening. The formalin-inactivated whole-cell vaccine (WCV) confers long-term protection but has significant side effects when administered to presensitized individuals. Designing new vaccines against C. burnetii remains a challenge and requires the use of clinically relevant modes of transmission in appropriate animal models. We have developed a safe and reproducible C. burnetii aerosol challenge in three different animal models to evaluate the effects of pulmonary acquired infection. Using a MicroSprayer aerosolizer, BL/6 mice and Hartley guinea pigs were infected intratracheally with C. burnetii Nine Mile phase I (NMI) and demonstrated susceptibility as determined by measuring bacterial growth in the lungs and subsequent dissemination to the spleen. Histological analysis of lung tissue showed significant pathology associated with disease, which was more severe in guinea pigs. Infection using large-particle aerosol (LPA) delivery was further confirmed in nonhuman primates, which developed fever and pneumonia. We also demonstrate that vaccinating mice and guinea pigs with WCV prior to LPA challenge is capable of eliciting protective immunity that significantly reduces splenomegaly and the bacterial burden in spleen and lung tissues. These data suggest that these models can have appreciable value in using the LPA delivery system to study pulmonary Q fever pathogenesis as well as designing vaccine countermeasures to C. burnetii aerosol transmission.

scholarly journals Dystrophic Mineralization of Costal Cartilage in Hartley Guinea Pigs

2016 ◽  
Vol 45 (3) ◽  
pp. 435-439
Author(s):  
Alexandria M. Schauer ◽  
Adrienne Schucker ◽  
Cathy S. Carlson
Keyword(s):  
Skeletal Muscle ◽  
Bone Marrow ◽  
Animal Models ◽  
Cross Sections ◽  
Guinea Pigs ◽  
Incidental Findings ◽  
Costal Cartilage ◽  
Osseous Metaplasia ◽  
Animal Models Of Disease ◽  
Models Of Disease

Hartley guinea pigs are widely used animal models of disease, particularly in studies of osteoarthritis. The purpose of this study was to investigate lesions in the costal cartilage from 16 male, 5- to 6-month-old Hartley guinea pigs. Routine histological sections from the costal cartilage and costochondral junction (longitudinal and cross sections) and sternum (for evaluation of bone marrow) were examined. All 16 (100%) animals had histological lesions involving the costal cartilage that included matrix degeneration and mineralization, reduced cellularity, and evidence of chondrocyte necrosis. Of the 16, 4 (25%) of the lesions contained blood vessels and 3 (19%) contained central osseous metaplasia. The cartilage lesions were accompanied by degeneration (sometimes with regeneration and/or fibrosis) in adjacent skeletal muscle in 15 of the 16 (94%) animals. The lesions in the costal cartilage were interpreted as dystrophic mineralization of unknown cause and appear to be incidental findings, although they bear some resemblance to lesions occurring in Tietze’s disease in humans. The significance of the lesions in skeletal muscle is unclear. Histological lesions of cartilage matrix degeneration and mineralization in these sites have not, to our knowledge, been reported previously.

scholarly journals Generation of Attenuated Mycobacterium bovis Strains by Signature-Tagged Mutagenesis for Discovery of Novel Vaccine Candidates

2005 ◽  
Vol 73 (4) ◽  
pp. 2379-2386 ◽  
Author(s):  
Desmond M. Collins ◽  
Bronwyn Skou ◽  
Stefan White ◽  
Shalome Bassett ◽  
Lauren Collins ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Guinea Pigs ◽  
Essential Role ◽  
Immunoblot Analysis ◽  
Infection Model ◽  
Vaccine Candidates ◽  
Mouse Infection Model ◽  
Potential Vaccine

ABSTRACT Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex, has a particularly wide host range and causes tuberculosis in most mammals, including humans. A signature tag mutagenesis approach, which employed illegitimate recombination and infection of guinea pigs, was applied to M. bovis to discover genes important for virulence and to find potential vaccine candidates. Fifteen attenuated mutants were identified, four of which produced no lesions when inoculated separately into guinea pigs. One of these four mutants had nine deleted genes including mmpL4 and sigK and, in guinea pigs with aerosol challenge, provided protection against tuberculosis at least equal to that of M. bovis BCG. Seven mutants had mutations near the esxA (esat-6) locus, and immunoblot analysis of these confirmed the essential role of other genes at this locus in the secretion of EsxA (ESAT-6) and EsxB (CFP10). Mutations in the eight other attenuated mutants were widely spread through the chromosome and included pks1, which is naturally inactivated in clinical strains of M. tuberculosis. Many genes identified were different from those found by signature tag mutagenesis of M. tuberculosis by use of a mouse infection model and illustrate how the use of different approaches enables identification of a wider range of attenuating mutants.

scholarly journals Pathogenesis and Animal Models of Post-Primary (Bronchogenic) Tuberculosis, A Review

Pathogens ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 19 ◽  
Author(s):  
Robert Hunter ◽  
Jefrey Actor ◽  
Shen-An Hwang ◽  
Arshad Khan ◽  
Michael Urbanowski ◽  
...  
Keyword(s):  
Animal Models ◽  
Guinea Pigs ◽  
Systemic Infection ◽  
Targeted Therapeutics ◽  
Animal Tissues ◽  
Caseation Necrosis ◽  
New Hosts ◽  
Bronchial Infection ◽  
Host Parasite ◽  
Modern Technologies

Primary and post-primary tuberculosis (TB) are different diseases caused by the same organism. Primary TB produces systemic immunity. Post-primary TB produces cavities to support massive proliferation of organisms for transmission of infection to new hosts from a person with sufficient immunity to prevent systemic infection. Post-primary, also known as bronchogenic, TB begins in humans as asymptomatic bronchial spread of obstructive lobular pneumonia, not as expanding granulomas. Most lesions regress spontaneously. However, some undergo caseation necrosis that is coughed out through the necrotic bronchi to form cavities. Caseous pneumonia that is not expelled through the bronchi is retained to become the focus of fibrocaseous disease. No animal reproduces this entire process. However, it appears that many mammals utilize similar mechanisms, but fail to coordinate them as do humans. Understanding this makes it possible to use human tuberculous lung sections to guide manipulation of animals to produce models of particular human lesions. For example, slowly progressive and reactivation TB in mice resemble developing human bronchogenic TB. Similarly, bronchogenic TB and cavities resembling those in humans can be induced by bronchial infection of sensitized rabbits. Granulomas in guinea pigs have characteristics of both primary and post primary TB. Mice can be induced to produce a spectrum of human like caseating granulomas. There is evidence that primates can develop bronchogenic TB. We are optimistic that such models developed by coordinated study of human and animal tissues can be used with modern technologies to finally address long-standing questions about host/parasite relationships in TB, and support development of targeted therapeutics and vaccines.

scholarly journals MTSA-10, the Product of the Rv3874 Gene of Mycobacterium tuberculosis, Elicits Tuberculosis-Specific, Delayed-Type Hypersensitivity in Guinea Pigs

2000 ◽  
Vol 68 (2) ◽  
pp. 990-993 ◽  
Author(s):  
Roberto Colangeli ◽  
John S. Spencer ◽  
Pablo Bifani ◽  
Alan Williams ◽  
Konstantin Lyashchenko ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Mycobacterium Avium ◽  
Guinea Pigs ◽  
Nontuberculous Mycobacteria ◽  
Specific Antigen ◽  
Delayed Type Hypersensitivity ◽  
New Skin

ABSTRACT In a search for new skin test reagents specific for tuberculosis, we found that the antigen encoded by gene Rv3874 of Mycobacterium tuberculosis elicited delayed-type hypersensitivity in M. tuberculosis-infected guinea pigs but not in control animals immunized with Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium avium. The antigen, which was named MTSA-10 (for M. tuberculosis-specific antigen 10), is a prime candidate for a component of a new tuberculin that will allow discrimination by a skin test of latent M. tuberculosis infection from vaccination with BCG or from sensitization with environmental, nontuberculous mycobacteria.

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