Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe.

BACKGROUND: The replication-competent recombinant vesicular stomatitis virus (rVSV)-based vaccine expressing a Zaire ebolavirus (ZEBOV) glycoprotein was selected for rapid safety and immunogenicity testing before its use in West Africa. METHODS: We performed three open-label, dose-escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial to assess the safety, side-effect profile, and immunogenicity of rVSV-ZEBOV at various doses in 158 healthy adults in Europe and Africa. All participants were injected with doses of vaccine ranging from 300,000 to 50 million plaque-forming units (PFU) or placebo. RESULTS: No serious vaccine-related adverse events were reported. Mild-to-moderate early-onset reactogenicity was frequent but transient (median, 1 day). Fever was observed in up to 30% of vaccinees. Vaccine viremia was detected within 3 days in 123 of the 130 participants (95%) receiving 3 million PFU or more; rVSV was not detected in saliva or urine. In the second week after injection, arthritis affecting one to four joints developed in 11 of 51 participants (22%) in Geneva, with pain lasting a median of 8 days (interquartile range, 4 to 87); 2 self-limited cases occurred in 60 participants (3%) in Hamburg, Germany, and Kilifi, Kenya. The virus was identified in one synovial-fluid aspirate and in skin vesicles of 2 other vaccinees, showing peripheral viral replication in the second week after immunization. ZEBOV-glycoprotein-specific antibody responses were detected in all the participants, with similar glycoprotein-binding antibody titers but significantly higher neutralizing antibody titers at higher doses. Glycoprotein-binding antibody titers were sustained through 180 days in all participants. CONCLUSIONS: In these studies, rVSV-ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy. (Funded by the Wellcome Trust and others; ClinicalTrials.gov numbers, NCT02283099, NCT02287480, and NCT02296983; Pan African Clinical Trials Registry number, PACTR201411000919191.)

Volunteer feedback and perceptions after participation in a phase I, first-in-human Ebola vaccine trial: An anonymous survey

The continued participation of volunteers in clinical trials is crucial to advances in healthcare. Few data are available regarding the satisfaction and impressions of healthy volunteers after participation in phase I trials, many of which lead to unexpected adverse events. We report feedback from over 100 adult volunteers who took part in a first-in-human trial conducted in a high-income country testing an experimental Ebola vaccine causing significant reactogenicity, as well as unexpected arthritis in one fifth of participants. The anonymous, internet-based satisfaction survey was sent by email to all participants upon their completion of this one-year trial; it asked 24 questions concerning volunteers' motivations, impressions of the trial experience, and overall satisfaction. Answers were summarized using descriptive statistics. Of the 115 trial participants, 103 (90%) filled out the survey. Fifty-five respondents (53%) were male. Thirty-five respondents (34%) were healthcare workers, many of whom would deploy to Ebola-affected countries. All respondents cited scientific advancement as their chief motivation for participation, while 100/103 (97%) and 61/103 (59%) reported additional "humanitarian reasons" and potential protection from Ebolavirus, respectively. Although investigators had documented adverse events in 97% of trial participants, only 74 of 103 respondents (72%) recalled experiencing an adverse event. All reported an overall positive experience, and 93/103 (90%) a willingness to participate in future trials. Given the high level of satisfaction, no significant associations could be detected between trial experiences and satisfaction, even among respondents reporting adverse events lasting weeks or months. Despite considerable reactogenicity and unexpected vaccine-related arthritis, all survey respondents reported overall satisfaction. While this trial's context was unique, the positive feedback is likely due at least in part to the intense communication of trial information to participants, which included both general findings and personalized results

Ebola: le point au crépuscule d'une épidémie inattendue

In one year, Ebola virus disease has already been responsible of around 10000 deaths. 24 patients have been medically evacuated in different University Hospitals in Europe or in the United States. One medical doctor, infected during a humanitarian mission in the field has been treated in Geneva at the end of 2014. This review aims to summarize the epidemiology of the current outbreak, to describe the main virological and clinical characteristics of Ebola virus disease, and to address the most important experimental treatments available. Although the number of cases has fallen the last two months, the outbreak is not over. A safe and proctective vaccine is still needed in the race to fight this emerging viral disease.La maladie à virus Ebola sévissant actuellement en Afrique de l’Ouest a fait près de 10 000 morts en une année. 24 patients ont été rapatriés en Europe ou aux Etats-Unis. Un médecin infecté sur le terrain au cours d’une mission humanitaire a été pris en charge aux Hôpitaux universitaires de Genève à la fin de l’année 2014. Cette revue a pour but de faire le point sur l’épidémiologie actuelle, d’exposer les principales caractéristiques virologiques, physiopathologiques, cliniques et diagnostiques de la maladie, et d’aborder les possibilités thérapeutiques. Bien que les derniers rapports épidémiologiques soient rassurants, l’épidémie n’est pas encore sous contrôle. Le développement d’un vaccin efficace et sûr reste nécessaire pour éviter une nouvelle crise humanitaire d’une telle ampleur

Survey respondents’ perceptions of the trial’s conduct.

<p>Detailed responses including free-text comments can be found online (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0173148#pone.0173148.s001" target="_blank">S1 File</a>).</p

Baseline characteristics reported by respondents.

<p>Of 115 trial volunteers, 103 (90%) completed the survey.</p

The trial flowchart with corresponding numbers of trial and survey participants.

<p>Because the survey was conducted anonymously, exact doses received by vaccinee respondents are unknown.</p

Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone

Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone

Clinical features and viral kinetics in a rapidly cured patient with Ebola virus disease: a case report

A detailed description of viral kinetics, duration of virus shedding, and intraviral evolution in different body sites is warranted to understand Ebola virus pathogenesis. Patients with Ebola virus infections admitted to university hospitals provide a unique opportunity to do such in-depth virological investigations. We describe the clinical, biological, and virological follow-up of a case of Ebola virus disease