We are very pleased to present to you in this newsletter edition the research partner profiles of the 3 clinical sites involved in the VSV-EBOVAC project: the University of Geneva, the Centre de Recherches Médicales de Lambaréné and the KEMRI/Wellcome Trust Research Programme.
The University of Geneva (UNIGE) is the academic hub of the University Hospitals of Geneva (HUG), which in turn is Switzerland’s largest academic hospital network. Comprised of eight hospitals and roughly 40 outpatient clinics, the HUG came into existence in 1995 with the merger of all public health facilities in the Swiss canton of Geneva. The network has over 10,000 employees and more than 1700 inpatient beds, managing roughly 60,000 hospital admissions per year.
UNIGE’s Centre for Vaccine Immunology (CVI) has been conducting vaccine research since 2000, in direct collaboration with other academic centres in over thirteen countries and as a World Health Organisation Collaborating Centre. The CVI occupies > 150m2 of fully equipped research laboratories, including a P2 laboratory and access to spf/P2 animal facilities.
In collaboration with the HUG’s Infectious Disease Division and Clinical Trials Unit (Centre de Recherche Clinique, CRC), the CVI conducted the phase I, first-in-human randomized controlled trial, testing the VSV-ZEBOV vaccine in healthy volunteers in 2014-2015. The samples from these vaccinees, as well as those from the phase I trials in Lambaréné, Gabon, and Kilifi, Kenya, now form the basis of the ongoing research of the VSV-EBOVAC Consortium. In the VSV-EBOVAC project, the key UNIGE tasks are (1) to characterize the innate responses elicited by various doses of VSV-ZEBOV and to define innate correlates with viral control, vaccine reactogenicity and antibody responses in the samples from the Geneva trial, (2) to perform a detailed characterization of antibody responses elicited by VSV-ZEBOV, and (3) to perform a direct comparison of the long-term immunity (antibody, memory B cells, CD8 and CD4 T cell) generated after Ebola infection versus that generated in volunteers vaccinated with the VSV-ZEBOV vaccine.
The Geneva phase I trial was extended to twelve months in order to assess humoral immune responses one year after vaccination and to continue long-term clinical monitoring; it terminated successfully in March 2016. A prospective observational study was recently launched; its goal is to further follow the roughly 100 vaccinees over the next four years for further assessment of immune durability as well as continued exploratory analyses as described above.
In the meantime, UNIGE and other VSV-EBOVAC members have begun their extensive characterisation of the innate responses elicited by various VSV-ZEBOV doses: a plasma signature composed of two chemokines and four cytokines has been identified. This signature was derived from the samples from Geneva vaccinees and validated—with strong correlation—against samples from Lambaréné vaccinees. The first of its kind to be identified, the signature correlates strongly with reactogenicity and later immunogenicity. Results are under review for publication.
Dr. Lemaître and Dr. Yerly at work (a, b). First Geneva phase I volunteer vaccination (c). Professor Claire-Anne Siegrist describes the phase I VSV-ZEBOV trial to reporters (d).
Centre de Recherches Médicales de Lambaréné (CERMEL) was established in 1981 at the Albert Schweitzer Hospital (ASH) in Lambaréné, in the rural province of Moyen Ogoué, Gabon. It has established itself as a center of excellence for research with special focus on tropical diseases such as malaria, schistosomiasis, filariasis and helminths and recently the interest for infection diseases as TB, HIV and other neglected tropical diseases (NTDs). Centre de Recherches Médicales de Lambaréné
CERMEL is integrated in the routine services of the ASH and is offering diagnostic and treatment follow up services to both patients consulting directly from Lambaréné and patients referred by collaborating governmental hospitals.
CERMEL is entirely self-financed through research projects and external grants. Current and past funders include the European Union, the Medical Faculty of the University of Tübingen, the German Ministry of Research, the US National Institute of Health, WHO/TDR, and pharmaceutical companies. More details on CERMEL can be found here.
Clinical research at CERMEL is supported by specialized laboratory departments-Fundamental Research, Microbiology and a Mycobacteriology.
The role of CERMEL in the VSV-EBOVAC project is to conduct phase I and phase II trials in Lambaréné. Within the phase I trial, CERMEL accrues safety data in adults and children over an extended period of 5 years. In addition to conducting the phase I trial, CERMEL will provide samples for immunological assessments for the five years of follow-up. Furthermore, CERMEL conducts a phase II pediatric trial to provide more safety and immunological assessment in children 6 months to 17 years. Samples collected by CERMEL are being shared with other VSV-EBOVAC partners to characterize the correlates of immunity and the transcriptomic and metabolomic signatures of the response to the VSV-ZEBOV vaccination.
Vaccination in Cermel and Albert Schweitzer Hospital (ASH) in Lambaréné.
The KEMRI|Wellcome Trust Research Programme is a world renowned health research unit of excellence. The programme was formed in 1989 when the Kenya Medical Research Institute formed a partnership with the Wellcome Trust and the University of Oxford. Over the last 26 years, the Programme has grown from a small group of 12 to a state of the art facility hosting over 100 research scientists and 700 support staff working across Kenya, Uganda and the region. KEMRI has over the years excelled in use of novel ideas working with local community’s to achieve better health for Africa while also developing African scientific leaders. Read more on KEMRI|Wellcome Trust Research Programme here.
The VSV-EBOVAC project benefits from having access to the clinical samples of subjects, who were vaccinated with different doses of the VSV-ZEBOV vaccine, originated from the clinical trial conducted at the KEMRI site “A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Immunogenicity of the BPSC1001 (VSVΔG-ZEBOV) Ebola Virus Vaccine Candidate in Healthy Adult Volunteers in Kilifi, Kenya” (NCT02296983).
Samples collected in KEMRI are shared with project partners involved in characterization of the correlates of immunity to the rVSV-ZEBOV vaccine and in the transcriptomic and metabolomic studies.
County Hospital in Kilifi