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At least 19 recordsLinked to original sources
PubMed2026

Construction and characterization of novel Mycobacterium tuberculosis-derived triple and quadruple knockout vaccines against tuberculosis.

Tuberculosis (TB) is a deadly disease that claims the lives of over a million people each year worldwide. The Bacille Calmette-Guérin vaccine has long been used to protect against TB, but it produces variable effects across different populations and fails to protect against adult pulmonary TB. Therefore, there is an urgent need for alternative vaccines that can offer better protection. We have developed a strategy for the rational deletion of virulence-related genes in Mycobacterium tuberculosis (Mtb) to create hyperattenuation that also enhances immunogenicity. Previously, we generated both single (∆fbpA) and double knockout (DKO) (∆fbpA-∆sapM) mutants of Mtb and assessed their immunogenicity and efficacy using mice. Herein, we have created triple knockout (TKO) and quadruple knockout (QKO) strains to enhance the immunogenicity and safety of the DKO strain by deleting the zmp1 and dosR genes. The resulting TKO strains, TKO-Z (∆fbpA-∆sapM-∆zmp1) and TKO-D (∆fbpA-∆sapM-∆dosR), and the QKO strain (∆fbpA-∆sapM-∆zmp1-∆dosR), were evaluated for their immunogenicity and safety in mice. Whereas TKO-Z and QKO strains exhibited superior immunogenicity compared to the DKO strain, their protective efficacy in mice was comparable. However, survival studies involving SCID mice indicated that the QKO strain was highly attenuated. Therefore, rational deletion of genes in Mtb seems to be an innovative approach for developing safer and more efficacious vaccines against TB.

Animals↗
PubMed1975

[Data obtained in more than 20 years of extensive use of Salvioli's diffusing anti-tuberculosis killed vaccine in Bologna].

V.D.S. (Killed T.B. vaccine, Salvioli disperdent) has been administered intradermally to the newborn in Bologna for over 20 yr. It causes a distinct reaction, lasting several weeks, in the injection site and its associated tissues. The alllergy thus constituted is evidence of a highly effective, timely and lasting defence reaction, accompanied by a marked increase in paraspecific reactivity directed to various other sources of infection. These features have been observed and recorded over the long period in which V.D.S. has been widely employed in voluntary vaccination of the newborn in Bologna.

Age Factors↗
PubMed1978

Pre-morbid factors in Hodgkin's disease. II. BCG-vaccination status, tuberculosis, infectious diseases, tonsillectomy, and appendectomy.

In young adults with Hodgkin's disease, cell mediated immunity (CMI) was evaluated retrospectively from their health records. The register of records from the school health service of the Copenhagen Council was scrutinized in order to find the records of those with HD born between 1930 and 1950 in whom the disease had been diagnosed between 1943 and 1975. Whenever possible, three controls were selected from the register for each case; they were comparable in respect of sex, year and month of birth and socio-economic background. The material consisted of 63 cases and 182 controls. Information regarding BCG-vaccinations, tuberculin skin-tests, the frequency of tuberculosis, bacterial and viral diseases, and of tonsilectomy, adenoidectomy and appendectomy was obtained from the school health records. 2 HD patients have had tuberculosis versus none in the control group. Complications to or prolonged course of viral diseases were reported neither in HD patients nor in controls. No significant differences were found in the frequency of BCG-vaccination, tuberculin reactivity, viral and bacterial diseases, adenoidectomy, tonsilectomy and appendectomy. Therefore our findings do not support the concept of a pre-morbid CMI deficiency state in HD.

Adenoidectomy↗
PubMed2025

Global biological sample collections from tuberculosis studies: a scoping review.

Progress in tuberculosis vaccine development is hindered by the incomplete understanding of protective immunity and other disease mechanisms. An interconnected network of sample biorepositories from tuberculosis studies could help to address these gaps. To assess the feasibility of such a resource, we conducted a scoping review of tuberculosis observational studies and vaccine clinical trials. The included studies collected at least one biological sample from tuberculosis cases, contacts, or controls and had more than 100 participants. We contacted the corresponding authors of these studies to determine the sample availability and interest in interconnected biorepositories. For the period 2014-24, we identified 104 observational studies and 18 vaccine trials that collected biological samples from 35 075 tuberculosis cases, 39 450 contacts or controls, and 45 628 trial participants across 43 countries. The commonly collected samples were blood, human genomic DNA, RNA, and sputum. Interest among the contacted investigators was high. Interconnected sample biorepositories could facilitate large-scale investigations and accelerate progress towards tuberculosis vaccine development.

Humans↗
PubMed1977

Transfer of delayed hypersensitivity in mice to microbial antigens with dialyzable transfer factor.

Dialyzable Lawrence-type transfer factor was prepared from the spleen cells of CF1 mice inoculated with Coccidioides immitis- and Candida albicans-killed vaccines and with live Mycobacterium tuberculosis vaccine (BCG). These preparations were shown to transfer antigen-specific cell-mediated immunity to naive mice, as measured by the delayed skin test and footpad-swelling methods. Reactivity could be demonstrated when the test antigens were given 24 h after the transfer factor, but not when they were given simultaneously. Coccidioides-specific transfer factor was shown to be sensitive to Pronase and resistant to trypsin and ribonuclease. A preparation of BCG transfer factor was sensitive to snake venom phosphodiesterase.

Animals↗
PubMed1977

[The influence of BCG-vaccination on the tuberculosis in children (Hamburg 1950-1971) (author's transl)].

Between 1950 to 1971 6 758 cases of active tuberculosis were registered among children under 15 years of age in Hamburg. 33 of them died, mostly due to tuberculous meningitis. In spite of a general decrease in tuberculosis during that period a relative increase of cases of pleurisy, nodular tuberculosis and tuberculous infiltrations of the lung were seen. On the other hand, cases of tuberculous meningitis and miliary tuberculosis as well as cases of glandular tuberculosis decreased. Rarely BCG-vaccinated children suffered from miliary tuberculosis, tuberculous meningitis and pleurisy. A statistical comparison between BCG-vaccinated and unvaccinated children of the birth cohorts 1954 and 1963 revealed that unvaccinated children suffered significantly more often from tuberculosis than the vaccinated. The duration of the protection by BCG-vaccination has been calculated for 7 years. BCG-vaccination after school age of the tuberculin negative persons is still debatable.

Adolescent↗
PubMed1975

Tuberculosis notwithstanding BCG vaccination.

In a series of 176 patients, 40 children (23%) developed tuberculosis notwithstanding BCG vaccination. The type and severity of the disease in this group were similar to those of the larger series of which this group was a part. However, BCG vaccination appeared to diminish the incidence of dissemination, especially tuberculous meningitis, and the number of deaths. The 40% incidence of tuberculous contacts probably indicates heavy exposure to infection. BCG offers a modicum of protection which the vulnerable should not be denied, but its use should not lead to complacency--the potency of vaccines and the technique of vaccination require constant surveillance. Case finding remains a priority and even BCG-vaccinated patients should be treated for tuberculosis when this is suspected.

BCG Vaccine↗