Live-attenuated Mycobacterium tuberculosis vaccine MTBVAC versus BCG in adults and neonates: a randomised controlled, double-blind dose-escalation trial

Background: Infants are a key target population for new tuberculosis vaccines. We assessed the safety and immunogenicity of the live-attenuated Mycobacterium tuberculosis vaccine candidate MTBVAC in adults and infants in a region where transmission of tuberculosis is very high. Methods: We did a randomised, double-blind, BCG-controlled, dose-escalation trial at the South African Tuberculosis Vaccine Initiative site near Cape Town, South Africa. Healthy adult community volunteers who were aged 18–50 years, had received BCG vaccination as infants, were HIV negative, had negative interferon-¿ release assay (IGRA) results, and had no personal history of tuberculosis or current household contact with someone with tuberculosis were enrolled in a safety cohort. Infants born to HIV-negative women with no personal history of tuberculosis or current household contact with a person with tuberculosis and who were 96 h old or younger, generally healthy, and had not yet received routine BCG vaccination were enrolled in a separate infant cohort. Eligible adults were randomly assigned (1:1) to receive either BCG Vaccine SSI (5 × 105 colony forming units [CFU] of Danish strain 1331 in 0·1 mL diluent) or MTBVAC (5 × 105 CFU in 0·1 mL) intradermally in the deltoid region of the arm. After favourable review of 28-day reactogenicity and safety data in the adult cohort, infants were randomly assigned (1:3) to receive either BCG Vaccine SSI (2·5 × 105 CFU in 0·05 mL diluent) or MTBVAC in three sequential cohorts of increasing MTBVAC dose (2·5 × 103 CFU, 2·5 × 104 CFU, and 2·5 × 105 CFU in 0·05 mL) intradermally in the deltoid region of the arm. QuantiFERON-TB Gold In-Tube IGRA was done on days 180 and 360. For both randomisations, a pre-prepared block randomisation schedule was used. Participants (and their parents or guardians in the case of infant participants), investigators, and other clinical and laboratory staff were masked to intervention allocation. The primary outcomes, which were all measured in the infant cohort, were solicited and unsolicited local adverse events and serious adverse events until day 360; non-serious systemic adverse events until day 28 and vaccine-specific CD4 and CD8 T-cell responses on days 7, 28, 70, 180, and 360. Secondary outcomes measured in adults were local injection-site and systemic reactions and haematology and biochemistry at study day 7 and 28. Safety analyses and immunogenicity analyses were done in all participants who received a dose of vaccine. This trial is registered with ClinicalTrials.gov, number NCT02729571. Findings: Between Sept 29, 2015, and Nov 16, 2015, 62 adults were screened and 18 were enrolled and randomly assigned, nine each to the BCG and MTBVAC groups. Between Feb 12, 2016, and Sept 21, 2016, 36 infants were randomly assigned—eight to the BCG group, nine to the 2·5 × 103 CFU MTBVAC group, nine to the 2·5 × 104 CFU group, and ten to the 2·5 × 105 CFU group. Mild injection-site reactions occurred only in infants in the BCG and the 2·5 × 105 CFU MTBVAC group, with no evidence of local or regional injection-site complications. Systemic adverse events were evenly distributed across BCG and MTBVAC dose groups, and were mostly mild in severity. Eight serious adverse events were reported in seven vaccine recipients (one adult MTBVAC recipient, one infant BCG recipient, one infant in the 2·5 × 103 CFU MTBVAC group, two in the 2·5 × 104 CFU MTBVAC group, and two in the 2·5 × 105 CFU MTBVAC group), including one infant in the 2·5 × 103 CFU MTBVAC group treated for unconfirmed tuberculosis and one in the 2·5 × 105 CFU MTBVAC group treated for unlikely tuberculosis. One infant died as a result of possible viral pneumonia. Vaccination with all MTBVAC doses induced durable antigen-specific T-helper-1 cytokine-expressing CD4 cell responses in infants that peaked 70 days after vaccination and were detectable 360 days after vaccination. For the highest MTBVAC dose (ie, 2·5 × 105 CFU), these responses exceeded responses induced by an equivalent dose of the BCG vaccine up to 360 days after vaccination. Dose-related IGRA conversion was noted in three (38%) of eight infants in the 2·5 × 103 CFU MTBVAC group, six (75%) of eight in the 2·5 × 104 CFU MTBVAC group, and seven (78%) of nine in the 2·5 × 105 CFU MTBVAC group at day 180, compared with none of seven infants in the BCG group. By day 360, IGRA reversion had occurred in all three infants (100%) in the 2·5 × 103 CFU MTBVAC group, four (67%) of the six in the 2·5 × 104 CFU MTBVAC group, and three (43%) of the seven in the 2·5 × 105 CFU MTBVAC group. Interpretation: MTBVAC had acceptable reactogenicity, and induced a durable CD4 cell response in infants. The evidence of immunogenicity supports progression of MTBVAC into larger safety and efficacy trials, but also confounds interpretation of tests for M tuberculosis infection, highlighting the need for stringent endpoint definition. Funding: Norwegian Agency for Development Cooperation, TuBerculosis Vaccine Initiative, UK Department for International Development, and Biofabri

Technology commercialization front-end framework : metallurgical industry

The development and commercialization of technologies within the metallurgical industry often spans a time-frame of decades. This paper proposes a managerial framework that aims at increasing the success rate and speed of technology commercialization within this industry, focusing on the front end of the process. A case study research strategy was applied, with an in-depth evaluation of two cases. The cases involved technologies that were developed by a metallurgical research and development organization. For each of the cases, secondary data was collected, followed by interviews. The data was evaluated, compared, and consolidated into a framework. For the technology development stages of concept development, and for research and development, important factors were identified that contribute to the successful development of technologies with the objective of commercialization. During concept development, the most important factor was determined to be the identification of the need or opportunity within the market, whereas the most important factors during research and development were determined to be the involvement of a project champion, a suitable team, and a potential implementer. The central driver of technology commercialization was identified to be the market, along with the fulfilment of a need or opportunity within the market.http://www.saimm.co.za/journal-papersam2020Graduate School of Technology Management (GSTM

Citrus black spot is absent in the Western Cape, Northern Cape and Free State Provinces

The South African citrus industry is strongly focused on exports and South Africa is a signatory member of both the World Trade Organisation Agreement on the application of Sanitary and Phytosanitary Measures and the International Plant Protection Convention. Citrus black spot, caused by Guignardia citricarpa, does not occur in all the South African citrus production areas and, therefore, South Africa has a responsibility to provide those trading partners that have identified G. citricarpa as a regulated pest with reliable information about the distribution of citrus black spot within South Africa. Detection surveys were conducted in citrus production areas in the Western Cape, Northern Cape and Free State Provinces and appropriate diagnostic protocols were used to ensure reliable detection of G. citricarpa. Trees in commercial orchards and home gardens on farms and in towns of 17, 9 and 5 magisterial districts in the Western Cape, Northern Cape and Free State Provinces, respectively, were sampled between 1995 and 2010. Fruit samples were taken during June and July, and leaf samples from November to January. None of the 3060 fruit and leaf samples collected during these surveys tested positive for G. citricarpa. Phyllosticta capitalensis, a non-pathogenic, ubiquitous, endophytic species was, however, detected during these surveys. In compliance with relevant International Standards for Phytosanitary Measures and based on the outcome of these official surveys, these three provinces in South Africa can be recognised as citrus black spot pest free areas

Citrus black spot is absent in the Western Cape, Northern Cape and Free State Provinces

CITATION: Carstens, E. et al. 2012. Citrus black spot is absent in the Western Cape, Northern Cape and Free State Provinces. South African Journal of Science, 108(7/8), Art. #876, doi: 10.4102/sajs.v108i7/8.876.The original publication is available at http://sajs.co.zaThe South African citrus industry is strongly focused on exports and South Africa is a signatory member of both the World Trade Organisation Agreement on the application of Sanitary and Phytosanitary Measures and the International Plant Protection Convention. Citrus black spot, caused by Guignardia citricarpa, does not occur in all the South African citrus production areas and, therefore, South Africa has a responsibility to provide those trading partners that have identified G. citricarpa as a regulated pest with reliable information about the distribution of citrus black spot within South Africa. Detection surveys were conducted in citrus production areas in the Western Cape, Northern Cape and Free State Provinces and appropriate diagnostic protocols were used to ensure reliable detection of G. citricarpa. Trees in commercial orchards and home gardens on farms and in towns of 17, 9 and 5 magisterial districts in the Western Cape, Northern Cape and Free State Provinces, respectively, were sampled between 1995 and 2010. Fruit samples were taken during June and July, and leaf samples from November to January. None of the 3060 fruit and leaf samples collected during these surveys tested positive for G. citricarpa. Phyllosticta capitalensis, a non-pathogenic, ubiquitous, endophytic species was, however, detected during these surveys. In compliance with relevant International Standards for Phytosanitary Measures and based on the outcome of these official surveys, these three provinces in South Africa can be recognised as citrus black spot pest free areas.http://sajs.co.za/citrus-black-spot-absent-western-cape-northern-cape-and-free-state-provinces/carstens-elma-le-roux-hendrik-holtzhausen-michael-van-rooyen-liezl-coetzee-joey-wentzel-riaPublisher's versio

Citrus black spot is absent in the Western Cape, Northern Cape and Free State Provinces

The South African citrus industry is strongly focused on exports and South Africa is a signatory member of both the World Trade Organisation Agreement on the application of Sanitary and Phytosanitary Measures and the International Plant Protection Convention. Citrus black spot, caused by Guignardia citricarpa, does not occur in all the South African citrus production areas and, therefore, South Africa has a responsibility to provide those trading partners that have identified G. citricarpa as a regulated pest with reliable information about the distribution of citrus black spot within South Africa. Detection surveys were conducted in citrus production areas in the Western Cape, Northern Cape and Free State Provinces and appropriate diagnostic protocols were used to ensure reliable detection of G. citricarpa. Trees in commercial orchards and home gardens on farms and in towns of 17, 9 and 5 magisterial districts in the Western Cape, Northern Cape and Free State Provinces, respectively, were sampled between 1995 and 2010. Fruit samples were taken during June and July, and leaf samples from November to January. None of the 3060 fruit and leaf samples collected during these surveys tested positive for G. citricarpa. Phyllosticta capitalensis, a non-pathogenic, ubiquitous, endophytic species was, however, detected during these surveys. In compliance with relevant International Standards for Phytosanitary Measures and based on the outcome of these official surveys, these three provinces in South Africa can be recognised as citrus black spot pest free areas