VACCELERATE Site Network: Real-time definition of clinical study capacity in Europe

Background: The inconsistent European vaccine trial landscape rendered the continent of limited interest for vaccine developers. The VACCELERATE consortium created a network of capable clinical trial sites throughout Europe. VACCELERATE identifies and provides access to state-of-the-art vaccine trial sites to accelerate clinical development of vaccines. Methods: Login details for the VACCELERATE Site Network (vaccelerate.eu/site-network/) questionnaire can be obtained after sending an email to. Interested sites provide basic information, such as contact details, affiliation with infectious disease networks, main area of expertise, previous vaccine trial experience, site infrastructure and preferred vaccine trial settings. In addition, sites can recommend other clinical researchers for registration in the network. If directly requested by a sponsor or sponsor representative, the VACCELERATE Site Network pre-selects vaccine trial sites and shares basic study characteristics provided by the sponsor. Interested sites provide feedback with short surveys and feasibility questionnaires developed by VACCELERATE and are connected with the sponsor to initiate the site selection process. Results: As of April 2023, 481 sites from 39 European countries have registered in the VACCELERATE Site Network. Of these, 137 (28.5 %) sites have previous experience conducting phase I trials, 259 (53.8 %) with phase II, 340 (70.7 %) with phase III, and 205 (42.6 %) with phase IV trials, respectively. Infectious diseases were reported as main area of expertise by 274 sites (57.0 %), followed by any kind of immunosuppression by 141 (29.3 %) sites. Numbers are super additive as sites may report clinical trial experience in several indications. Two hundred and thirty-one (47.0 %) sites have the expertise and capacity to enrol paediatric populations and 391 (79.6 %) adult populations. Since its launch in October 2020, the VACCELERATE Site Network has been used 21 times for academic and industry trials, mostly interventional studies, focusing on different pathogens such as fungi, monkeypox virus, Orthomyxoviridae/influenza viruses, SARS-CoV-2, or Streptococcus pneumoniae/pneumococcus. Conclusions: The VACCELERATE Site Network enables a constantly updated Europe-wide mapping of experienced clinical sites interested in executing vaccine trials. The network is already in use as a rapid-turnaround single contact point for the identification of vaccine trials sites in Europe.The VACCELERATE Site Network has received funding from the European Union’s Horizon 2020 research and innovation pro gramme (grant agreement No 101037867) and the German Federal Ministry of Education and Research (Bundesministerium für Bil dung und Forschung [BMBF]) (grant agreement No BMBF01KX2040).S

Sequential Expression of Bacterial Virulence and Plant Defense Genes During Infection of Tomato with Clavibacter michiganensis subsp michiganensis

Chalupowicz L, Cohen-Kandli M, Dror O, et al. Sequential Expression of Bacterial Virulence and Plant Defense Genes During Infection of Tomato with Clavibacter michiganensis subsp michiganensis. PHYTOPATHOLOGY. 2010;100(3):252-261.The molecular interactions between Clavibacter michiganensis subsp. michiganensis and tomato plant were studied by following the expression of bacterial virulence and host-defense genes during early stages of infection. The C. michiganensis subsp. michiganensis genes included the plasmid-borne cellulase (celA) and the serine protease (pat-1), and the serine proteases chpC and ppaA, residing on the chp/tomA pathogenicity island (PAI). Gene expression was measured following tomato inoculation with Cmm382 (wild type), Cmm100 (lacking the plasmids pCM1 and pCM2), and Cmm27 (lacking the PAI). Transcriptional analysis revealed that celA and pat-1 were significantly induced in Cmm382 at initial 12 to 72 h, whereas chpC and ppaA were highly expressed only 96 h after inoculation. Interdependence between the expression of chromosomal and of plasmid-located genes was revealed: expression of celA and pat-1 was substantially reduced in the absence of the chp/tomA PAI, whereas chpC and ppaA expressions were reduced in the absence of the virulence plasmids. Transcription of chromosomal genes involved in cell wall degradation (i.e., pelA1, celB, xysA, and xysB), was also induced at early stages of infection. Expression of the host-defense genes, chitinase class II and pathogenesis-related protein-5 isoform was induced in the absence of the PAI at early stages of infection, suggesting that PAI-located genes are involved in suppression of tomato basal defenses

An Autoinhibitory Tyrosine Motif in the Cell-Cycle-Regulated Nek7 Kinase Is Released through Binding of Nek9

Mitosis is controlled by multiple protein kinases, many of which are abnormally expressed in human cancers. Nek2, Nek6, Nek7, and Nek9 are NIMA-related kinases essential for proper mitotic progression. We determined the atomic structure of Nek7 and discovered an autoinhibited conformation that suggests a regulatory mechanism not previously described in kinases. Additionally, Nek2 adopts the same conformation when bound to a drug-like molecule. In both structures, a tyrosine side chain points into the active site, interacts with the activation loop, and blocks the αC helix. Tyrosine mutants of Nek7 and the related kinase Nek6 are constitutively active. The activity of Nek6 and Nek7, but not the tyrosine mutant, is increased by interaction with the Nek9 noncatalytic C-terminal domain, suggesting a mechanism in which the tyrosine is released from its autoinhibitory position. The autoinhibitory conformation is common to three Neks and provides a potential target for selective kinase inhibitors

Mitotic kinases as regulators of cell division and its checkpoints

Mitosis and cytokinesis are undoubtedly the most spectacular parts of the cell cycle. Errors in the choreography of these processes can lead to aneuploidy or genetic instability, fostering cell death or disease. Here, I give an overview of the many mitotic kinases that regulate cell division and the fidelity of chromosome transmission

VACCELERATE Volunteer Registry: A European study participant database to facilitate clinical trial enrolment

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has evidenced the key role of vaccine design, obtention, production and administration to successfully fight against infectious diseases and to provide efficient remedies for the citizens. Although clinical trials were rapidly established during this pandemic, identifying suitable study subjects can be challenging. For this reason, the University Hospital Cologne established a volunteer registry for participation in clinical trials first in Germany, which has now been incorporated into the European VACCELERATE clinical trials network and grew to a European Volunteer Registry. As such, VACCELERATE's Volunteer Registry aims to become a common entry point for potential volunteers in future clinical trials in Europe. Methods: Interested volunteers who would like to register for clinical trials in the VACCELERATE Volunteer Registry can access the registration questionnaire via http://www.vaccelerate.eu/volunteer-registry. Potential volunteers are requested to provide their current country and area of residence, contact information, including first and last name and e-mail address, age, gender, comorbidities, previous SARS-CoV-2 infection and vaccination status, and maximum distance willing to travel to a clinical trial site. The registry is open to both adults and children, complying with national legal consent requirements. Results: As of May 2022, the questionnaire is available in 12 countries and 14 languages. Up to date, more than 36,000 volunteers have registered, mainly from Germany. Within the first year since its establishment, the VACCELERATE Volunteer Registry has matched more than 15,000 volunteers to clinical trials. The VACCELERATE Volunteer Registry will be launched in further European countries in the coming months. Conclusions: The VACCELERATE Volunteer Registry is an active single-entry point for European residents interested in COVID-19 clinical trials participation in 12 countries (i.e., Austria, Cyprus, Germany, Greece, Ireland, Lithuania, Norway, Portugal, Spain, Sweden and Turkey). To date, more than 15,000 registered individuals have been connected to clinical trials in Germany alone. The registry is currently in the implementation phase in 5 additional countries (i.e., Belgium, Czech Republic, Hungary, Israel and the Netherlands)

Enhancing public health communication of vaccine trials: The pan-European VACCELERATE Toolkit

Background: The pan-European VACCELERATE network aims to implement the first transnational harmonised and sustainable vaccine trial Volunteer Registry, serving as single entry-point for volunteers willing to participate in large scale vaccine clinical studies across the European region. The present work exhibits a set of harmonised vaccine trial educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. Objective: The main objectives of the present study are the design and creation of a standard toolkit to increase positive attitudes, and access to trustful information for better access and increased recruitment to vaccine trials for the public community. More specifically, the produced tools are focused on inclusiveness, equity, and they are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (elderly, migrants, children and adolescents). The promotion/education material is aligned with the main objectives of the Volunteer Registry, to increase public literacy and awareness regarding vaccine clinical research/trials and trial participation, such as informed consent and legal issues, side effects and frequently asked questions on vaccine trial design. Methods: The tools' development has followed the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity and they are adjusted to the local country requirements to improve public health communication. The selection of the produced tools has been based on the cognitive theory, inclusiveness and equity of different aged and under-represented groups, and standardised material from several official trustful sources (e.g. COVAX, ECDC, EUPATI, GAVI and WHO). In addition, team of specialists from different fields (infectious diseases, vaccine research, medicine, education) edited and reviewed the subtitles and scripts for the educational videos, extended brochures, interactive cards and puzzles. Graph designers also selected the colour palette, audio settings and dubbing for the video story-tales and implementation of QR codes. Results: This study presents the first set of harmonised promotional and educational materials/tools (i.e. educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (e.g. COVID-19). The developed tools inform the public about possible benefits and disadvantages of trial participation, but also build the confidence of participants about the safety and efficacy for COVID-19 vaccines and healthcare system. The present material has been translated into several languages and meant to be freely and easily accessible to facilitate dissemination among the participating countries of the VACCELERATE network, as well as among the European and global scientific, industrial, and public community, in general. Conclusions: The produced material could also be useful for filling knowledge gaps of healthcare personnel and providing the appropriate future patient education for vaccine trials, as well as to tackle vaccine hesitancy and parents' concerns for potential participation of children in vaccine trials