scholarly journals Identification of a Mycobacterium bovisBCG Auxotrophic Mutant That Protects Guinea Pigs against M. bovis and Hematogenous Spread of Mycobacterium tuberculosis without Sensitization to Tuberculin

2000 ◽  
Vol 68 (12) ◽  
pp. 7094-7099 ◽  
Author(s):  
Mark A. Chambers ◽  
Ann Williams ◽  
Dolores Gavier-Widén ◽  
Adam Whelan ◽  
Graham Hall ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Guinea Pigs ◽  
Insertional Mutagenesis ◽  
Severe Combined Immunodeficiency ◽  
Auxotrophic Mutant ◽  
Tuberculin Test ◽  
Live Attenuated Vaccine ◽  
Cutaneous Hypersensitivity ◽  
Immunodeficiency Disease

ABSTRACT Tuberculosis remains one of the most significant diseases of humans and animals. The only currently available vaccine against this disease is a live, attenuated vaccine, bacillus Calmette-Guérin (BCG), which was originally derived from Mycobacterium bovis and despite its variable efficacy is the most widely administered vaccine in the world. With the advent of the human immunodeficiency virus-AIDS pandemic concern has been raised over the safety of BCG. Moreover, since BCG sensitizes vaccinated individuals to the tuberculin test, vaccination with BCG prevents diagnosis of infection in vaccinated individuals. Recently, auxotrophic strains of BCG have been generated by insertional mutagenesis which have been shown to be safer than the parent BCG strain following administration to mice with severe combined immunodeficiency disease. These strains have also been shown to give comparable protection against intravenous and intratracheal challenge of BALB/c mice with M. tuberculosis relative to conventional BCG. Here we report that one of these mutants, a leucine auxotroph of BCG, conferred significant protection of the lungs and spleens of guinea pigs infected with M. bovis and protection of the spleens of guinea pigs infected with M. tuberculosis in the absence of a cutaneous hypersensitivity reaction to tuberculin. Therefore, protective immunity to tuberculosis may, at least in part, be achieved without sensitization to the tuberculin skin test. These results indicate that it may be possible to develop a new generation of vaccines based on BCG that are protective, are safe for use in the immunocompromised, and do not preclude the use of the tuberculin skin test in both humans and animals.

scholarly journals Use of Mycobacterium tuberculosisComplex-Specific Antigen Cocktails for a Skin Test Specific for Tuberculosis

1998 ◽  
Vol 66 (8) ◽  
pp. 3606-3610 ◽  
Author(s):  
Konstantin Lyashchenko ◽  
Claudia Manca ◽  
Roberto Colangeli ◽  
Anna Heijbel ◽  
Alan Williams ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Guinea Pigs ◽  
Nontuberculous Mycobacteria ◽  
Skin Testing ◽  
Specific Antigen ◽  
Diagnostic Value ◽  
Mycobacterial Species ◽  
Diagnostic Specificity ◽  
Single Antigen

ABSTRACT The tuberculin skin test currently used to diagnose infection withMycobacterium tuberculosis has poor diagnostic value, especially in geographic areas where the prevalence of tuberculosis is low or where the environmental burden of saprophytic, nontuberculous mycobacteria is high. Inaccuracy of the tuberculin skin test often reflects a low diagnostic specificity due to the presence in tuberculin of antigens shared by many mycobacterial species. Thus, a skin test specific for tuberculosis requires the development of new tuberculins consisting of antigens specific to M. tuberculosis. We have formulated cocktails of two to eight antigens of M. tuberculosis purified from recombinant Escherichia coli. Multiantigen cocktails were evaluated by skin testing guinea pigs sensitized with M. bovis BCG. Reactivity of multiantigen cocktails was greater than that of any single antigen. Cocktail activity increased with the number of antigens in the cocktail even when the same amount of total protein was used for cocktails and for each single antigen. A cocktail of four purified antigens specific for the M. tuberculosis complex elicited skin test responses only in BCG-immunized guinea pigs, not in control animals immunized with M. avium. These findings open the way to designing a multiantigen formulation for a skin test specific for tuberculosis.

Response of Tuberculin Skin Test to ACTH and Cortisone in Tuberculous Guinea Pigs

1950 ◽  
Vol 75 (2) ◽  
pp. 423-426 ◽  
Author(s):  
V. J. Derbes ◽  
J. H. Dent ◽  
N. K. Weaver ◽  
D. D. Vaughan
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Guinea Pigs

Reduced Genotoxic Risk Using Foamy Viral Vectors for the Treatment of Canine Leukocyte Adhesion Deficiency

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3744-3744
Author(s):  
Thomas R. Bauer ◽  
Mehreen Hai ◽  
Rima L. Adler ◽  
James M. Allen ◽  
Laura M. Tuschong ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Viral Vectors ◽  
Insertional Mutagenesis ◽  
Leukocyte Adhesion ◽  
Severe Combined Immunodeficiency ◽  
Insertion Site ◽  
Leukocyte Adhesion Deficiency ◽  
Hematopoietic Stem ◽  
Insertion Sites ◽  
Immunodeficiency Disease

Abstract Gammaretroviral vectors used in recent gene therapy clinical trials have lead to several successes, such as in the treatment of X-linked severe combined immunodeficiency disease, but have also resulted in insertional activation of nearby oncogenes, leading to leukemia in four patients. We previously reported the successful treatment of four dogs with canine leukocyte adhesion deficiency (CLAD), a lethal genetic immunodeficiency disease caused by defects in the leukocyte integrin CD18, by transplanting foamy viral (FV) vector (deltaphiMscv-cCD18) - transduced, autologous CD34+ hematopoietic stem cells. To date, more than 2 years post transplant, all four dogs have maintained CD18+ leukocyte levels ranging between 5–10%, completely reversing of the CLAD phenotype, and have no clinical or laboratory evidence of hematological malignancy. To assess the potential genotoxicity of the FV gene therapy in the treatment of CLAD, we compared the insertion sites (ISs) found in the FV vector treated CLAD dogs with ISs found in CLAD dogs treated by gammaretroviral (RV) vectors (PG13/Mscv-cCD18). Insertion sites were identified by DNA sequence analysis of ligation-mediated PCR (LM-PCR) or linear amplification-mediated PCR (LAM-PCR) amplicons and subsequent comparison to the dog genome (canFam 2.0, May 2005). Insertion site analysis was performed for integrations that were in or within 50 kb of Refseq genes (using mouse/human orthologs). Analysis of the ISs revealed a reduced preference for FV vector integrations near transcription start sites compared to RV vector integrations (41% vs. 48%), fewer integrations near potential oncogenes (11% vs. 16%), and fewer integrations within genes in general (41% vs. 52%), in the FV vector treated animals compared to the RV vector treated animals. These clinically relevant data suggest that a reduced insertional mutagenesis potential exists when using FV vectors compared to RV vectors, and support the use of FV vectors in the treatment of human hematopoietic stem cell diseases such as LAD.

scholarly journals Tuberculin reactivity in bacille calmette-guerin vaccinated individuals with sputum positive pulmonary tuberculosis

2012 ◽  
Vol 7 (1) ◽  
pp. 28-35
Author(s):  
PK Jha ◽  
R Gurung ◽  
N Gyawali ◽  
HP Nepal ◽  
DD Baral ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Tuberculin Test ◽  
Similar Rate ◽  
Sputum Smear ◽  
Healthy Individuals ◽  
Bacille Calmette Guerin ◽  
Pulmonary Tb ◽  
Sensitivity Rate ◽  
Apparently Healthy

The study was carried out to assess the value of tuberculin skin test for the diagnosis of Tuberculosis (TB) in BCG vaccinated individuals and to find out the sensitivity rate of tuberculin skin test (TST) in comparison to acid fast bacilli positive pulmonary TB. Similar population with high BCG vaccination coverage having both pulmonary TB patients (n=150) and apparently healthy individuals (n=150) in eastern Nepal were enrolled in this comparative study. Sputum from all the subjects was subjected to Z-N microscopy. TST was performed on these subjects by standard Mantoux method. Among the patients (mean age 36.18±14.15 yrs) and controls (mean age 35.61±13.44 yrs), 55.33 % and 47.33 % respectively have been found to be positive PPD reactors (>10mm) which is statistically not significant (P>0.05). About 23% of the patients & 27% of controls failed to react (anergic) to 5 TU PPD. PPD reactivity rate was high in the patients whose sputum smears were graded as 1+ in Z-N microscopy. The sensitivity of TST was highest for the induration of >5mm (77.3%). Specificity increased with increasing size of induration and was highest (73.3%) with induration of >15 mm. Tuberculin skin test is an all or none phenomenon. In Nepal, tuberculin test has a limited value in the diagnosis of pulmonary TB as both the apparently healthy individuals and patients with sputum smear positive pulmonary TB who had been immunized with BCG, showed almost similar rate of tuberculin reactivity. DOI: http://dx.doi.org/10.3126/jcmsn.v7i1.5970 JCMSN 2011; 7(1): 28-35

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