Vole Bacillus Research Articles

Efficacies of BCG and vole bacillus ( Mycobacterium microti) vaccines in preventing clinically apparent pulmonary tuberculosis in rabbits: a preliminary report

Tuberculosis (TB) kills more people in the world today than any other infectious disease, and the number of drug-resistant Mycobacterium tuberculosis isolates is increasing. Vaccines, better than most of the currently available strains of bacille Calmette–Guérin (BCG), are urgently needed to control this disease. TB in rabbits resembles human TB more closely than TB in any other common laboratory animal and a most pertinent method of assessing vaccine efficacy is Lurie's tubercle count method in this species. Vaccinated and control rabbits were infected by aerosol with virulent human-type tubercle bacilli (H37Rv). At necropsy 5 weeks thereafter, the grossly visible primary tubercles in the entire lung were counted. A decrease in the number of such tubercles is a quantitative measure of vaccine efficacy: An effective vaccine prevents microscopic tubercles from growing to grossly visible (clinically apparent) size. The Pasteur substrain of BCG and two substrains of Mycobacterium microti (the vole bacillus) reduced the number of visible primary tubercles an average of 75%, whereas three other substrains of BCG and three other substrains of vole bacilli only reduced the number an average of 40%. These initial studies indicate that Lurie's tubercle-count method in rabbits is a precise way to choose the best available tuberculosis vaccines.

Classics in infectious diseases: the relationship of "atypical" acid-fast bacteria to human disease: a preliminary report by Alice Timpe and Ernest H. Runyon.

Abstract Acid-fast organisms differing from known human or bovine tuberculosis strains have been isolated from eighty-eight patients. Although some appear to be intimately associated with pulmonary disease in man, none was virulent for guinea pigs inoculated with 1 mg. of organisms. It was possible to divide the organisms tentatively into three groups on the basis of colonial characteristics. Two of the groups (I and III) were found to be virulent for mice while the other was not. The taxonomic identity of the organisms described has not yet been established. Colonial and growth characteristics of the three groups are described. Certain of the strains show some resemblance to avian or vole bacilli. The organisms displaying mouse virulence are characterized by repeated occurrence over long periods of time iii sputa from the same patients, none of whom were found to have concurrent infection with M. tuberculosis . Seven of these strains were found directly in diseased human lung tissue. Twenty-four of these strains were tested for virulence in mice, and all caused lung lesions. On the other hand, seventeen strains of Group II showed no virulence for mice and were not as consistently associated with human disease. These organisms were found in lower concentration in original specimens and a greater proportion of them was isolated from gastric washings. Furthermore, several were from patients harboring typical tubercle bacilli as well. In the light of these findings, discard of an acid-fast organism isolated from a patient with pulmonary disease because it fails to fit the cultural or virulence pattern of M. tuberculosis does not appear justified.

Mycobacterium microti (Vole Bacillus): a Method for Viable Counts Within 21 Days of Culture

A method is described for counting viable units of Mycobacterium microti (vole bacillus) suspensions after 21 days of culture on an oleic-albumin agar medium containing 5% defibrinated horse blood, with a tight seal to maintain humidity. This method is important because vole bacillus is an alternative to BCG in the prevention of tuberculosis.

Statistical methods in clinical and preventive medicine.

This book is a collection of studies in which Professor Hill is the author or a co-author. They have been arranged into three sections: Clinical Trial of Treatment, Field Trial of Vaccines, and Epidemiological Approach. Each section begins with papers presenting the authors' view of the use of statistics as an aid in seeking answers to questions that arise in clinical and preventive medicine. Following the introductory papers in each section are several others which illustrate the use of statistics in particular investigations. Many of the papers are now regarded as classics by both medical investigators and statisticians. The papers include the trials of streptomycin versus bed-rest in the treatment of tuberculosis, cortisone versus aspirin in the treatment of rheumatoid arthritis, trials of B.C.G. and Vole Bacillus vaccines in the prevention of tuberculosis, and the famous studies of Doll and Hill on the relationship of smoking and carcinoma

B.C.G. and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescence and Early Adult Life

B.C.G. and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescence and Early Adult Life

The effects of vole bacillus vaccination of African mine workers in the Northern Rhodesian copper mines.

African mine workers exposed to siliceous dust in the metalliferous mines of Northern Rhodesia were tuberculin tested; of 17,697 tested, 13,667 were tuberculin positive and 4,030 negative. The negative reactors were divided at random into two approximately equal groups and 1,984 were vaccinated with vole bacillus vaccine and 2,046 were left unvaccinated. These two groups were subsequently followed up and their original radiological categories at the time of tuberculin testing and vaccination were compared with their radiological categories after varying periods of further dust exposure. The object of the investigation was to ascertain whether or not vaccination with vole bacillus vaccine introduced an acclerating factor in the rate of radiological change in pneumoconiosis. The results of the investigation showed that radiological changes in the two groups were minimal and that there was virtually no difference between them. No accelerated changes were recorded in the negative vaccinated group. This is regarded as evidence that anti-tuberculosis vaccine does not introduce an accelerating factor in pneumoconiosis. No case of pulmonary tuberculosis occurred in the negative vaccinated group. Three cases were recorded in the negative non-vaccinated group, suggesting that vaccination with vole bacillus vaccine affords some measure of protection against tuberculosis, and in view of the absence of any evidence that it had an accelerating effect in pneumoconiosis it appears desirable that miners should receive this protection.

The mycobacterium isolated from the dassie Procavia capensis (pallas)

Summary An acid-fast organism, referred to as the “dassie bacillus”, has been isolated from the Cape hyrax (dassie) in which it is believed to be the causative agent of pulmonary tuberculosis. The morphological and cultural properties of the dassie bacillus were not unlike those of the vole bacillus. On experimental inoculation into guinea-pigs, rabbits, mice, Mystromys albicaudatus, Rattus natalensis, and Tatera brantsi, it usually caused a local lesion with involvement of the regional nodes. Generalised infection was rare and in one instance only, a rabbit, the infection was lethal. No lesions were observed in infected domestic fowls. Immunological experiments showed that intravenous inoculation of mice with dassie bacilli had a retarding influence on infection following challenge with vole bacilli. However, all the animals ultimately succumbed to a caseating pneumonia. Preliminary treatment of guinea pigs with dassie bacilli also suggested a retarding effect on subsequent infection with small doses of myco. tuberculosis, var. bovis. The systematic position of the dassie bacillus is discussed and the opinion expressed that it may be classified either as an attenuated strain of the vole organism, or as an independent species of Mycobacterium.

Experimental Studies on the Morphology of Vole Bacillus Infection in Cattle, with a Contribution to the Development of So-Called Schaumann Bodies

Experimental Studies on the Morphology of Vole Bacillus Infection in Cattle, with a Contribution to the Development of So-Called Schaumann Bodies

B.C.G. and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescents: Second Report to the Medical Research Council

B.C.G. and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescents: Second Report to the Medical Research Council

The use of skin ulcer measurements to estimate immunity against tuberculosis in the guinea-pig

Summary Normal non-immune guinea-pigs after intradermal challenge with living vole bacilli develop ulcerated swellings which reach a maximum in about four weeks and then heal. Guinea-pigs vaccinated with BCG and then challenged with vole bacilli by the intradermal route also develop ulcerated swellings; but which are smaller, appear more rapidly and heal more quickly than in the non-immune animal. The speeds of development of hypersensitivity and immunity by the guinea-pig are reflected in the progress of these lesions and a comparison of their measurements in non-immune and vaccinated animals can be used for estimating the level of immunity. The comparison is more accurate if the effect of hypersensitivity is excluded and this was attempted by simultaneously challenging the animals in different sites with both killed and living vole bacilli. The measurements of the lesions produced by the ‘dead’ challenge were subtracted from those of the ‘living’ challenge and the resulting values were used in the assay. Using the technique described the method appears sensitive and precise. Statistically significant results can be obtained with a small number of animals and in a short time. The method therefore has advantages over mortality rate determinations.

スナネズミ (Meriones unguiculatus) の結核菌に対する感受性について

Susceptibility of variety of animals has been investigated in this laboratory. This paper is to report the experimental results with mongolian gerbile.Eighty-four mongolian gerbile (43 females and 41 males), aged 60 to 180 days, were used. The animals were from the colonies which had been raised in the National Institute of Health since 1952. Four strains of human type tubercle bacilli (one highly virulent, 2 moderately virulent, and 1 slightly virulent), four of bovine type (two highly virulent and 2 slightly virulent), and one of vole bacillus, 9 strains in all, were injected subcutaneously and tuberculin tests and tests for tuberculin shock were carried out.It was found that tuberculous infection took place in mongolian gerbile, which developed tubercl-es in lungs and other organs, although to a less extent than those in guinea pigs. No difffenerce was demonstrated between the animals received human type organisms and those received bovinetype ones. Injection of vole bacilli resulted in merely formation of localized abscess.Individual susceptibility was shown by the different appearance of changes even among those of the same age.No tuberculin skin reaction was perceived, while death from shock by tuberculin was observed.

Survival of vole bacilli in fresh and freeze-dried suspensions

Using either colony counts or direct microscopic counts to estimate viability, investigations have been made of the survival of both fresh and freeze-dried suspensions under different conditions of preparation and storage. Both types of product were preserved best at 4°C.; incubation at 37°C. was particularly destructive, especially for dried bacilli. Exposure to window light was rapidly lethal, the fresh preparations in this case being particularly susceptible. Aqueous 0·1 per cent albumin or human serum was a satisfactory suspending fluid for fresh preparations, but was completely inadequate for drying purposes, for which various fluids containing moderate concentrations (5–7·5 per cent) of glucose were most satisfactory. No influence of culture age on survival of freeze-dried suspensions could be demonstrated. Under optimal conditions of preparation and storage, viability of vole bacillus suspensions appeared to be at least equal to that of BCG. Fresh preparations were able to remain fully viable for more than a week and to retain 50 per cent viability after five weeks. Frozen-dried suspensions showed an initial fall to not less than 10 per cent generally 20–40 per cent, at which level most preparations remained for test periods of from six to nine months at 4° C.

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

<h3>ABSTRACT</h3> Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The panel of nanobodies were shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across many VoCs; wide-ranging epitopic and mechanistic diversity; high and broad <i>in vitro</i> neutralization potencies; and high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. <i>In vivo</i> protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to tackle current and future SARS-CoV-2 variants and SARS-related viruses. Furthermore, the high aerosol-ability of nanobodies provides the option for effective needle-free delivery through inhalation.

B.C.G. and Vole Bacillus Vaccines

B.C.G. and Vole Bacillus Vaccines

Observations on the growth and the enumeration of Vole Bacilli

The application of recently developed techniques for quantitative enumeration of total and viable tubercle bacilli to the study of vole bacilli has been examined and some incidental observations made on the growth and colonial variation of these organisms on oleic acid-albumin-agar medium. Total count estimations made in a Petroff-Hausser chamber were found to be reliable and easily performed even with highly dispersed suspensions provided that procedures involving grinding of the bacilli were avoided in their preparation. A technique for obtaining satisfactory dispersed suspensions free from bacterial debris is described. Some early difficulties with colony counts for estimating viable bacilli, carried out on oleic acid-albumin-agar medium, were resolved by ensuring adequate retention of moisture in culture plates by suitable sealing methods. The failure of strains, unadapted to this medium, to produce colonies in the absence of these precautions was probably attributable to their slower growth rate. Satisfactory procedures for sealing of culture plates are described. On plain oleic acid-albumin-agar medium the structure of the colony is a spreading one, intermediate between that of certain attenuated and of fully avirulent tubercle bacilli. No variation in this spreading morphology was observed but frequently there appeared two types of colony varying markedly in size, with the larger type in a distinct minority. Limited experimental studies suggest that the two ‘variants’ represented organisms with stable characteristics, probably differing in their growth rates in the semisynthetic medium. Provided culture plates are adequately sealed so that smaller colonies reach a countable size, the occasional presence of this colonial variation does not prevent a satisfactory application of the colony count method to the estimation of viable vole bacilli. Colony counts of freeze-dried, and sometimes of fresh, suspensions are increased by the inclusion of 5 per cent of whole blood in the solid medium. It is suggested that dried, and possibly undried, aged bacilli may have extra nutritional requirements supplied by blood. Alternatively, as most of the activity lies in the plasma fraction, the important factor may be protective rather than strictly nutritional. Disadvantages of the blood medium are its opacity and the failure of growing colonies to show a typical spreading morphology.

B.C.G. and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescents: First (Progress) Report to the Medical Research Council

B.C.G. and Vole Bacillus Vaccines in the Prevention of Tuberculosis in Adolescents: First (Progress) Report to the Medical Research Council

Enumeration of viable vole bacilli by direct Agar phase-contrast microscopsy

A problem encountered in estimating viability of the vole bacillus, J1!(ycobacterium tuberculosis val'. muris, by surface colony counts has been the inevitable delay with which final counts are obtained (Leach and Wells, 1956). At least four weeks' incubation is required even with strains adapted to optimal growth on oleic acid-albumin-agar medium, and furthermore this long incubation period is conducive to contamination, particularly by moulds which normally develop too slowly at 37°C. to affect cultures offaster-growing organisms. In order to overcome these difficulties an alternative method for estimating viability of vole bacilli was sought. Alternatives to the colony count method have been described for others of the mycobacteria, but these have relied mainly on such chemical procedures as the reduction of methylene blue (Cardoso and Almeida, 195I) or of tetrazolium dyes (Vandiviviere and others, 1952; Hanks, 1951). Such methods fail to give a count in terms of numbers or proportion of viable organisms and some method was required in which the proportion of bacteria capable of multiplying could be measured.