BackgroundIris scanning has increasingly been used for biometric identification over the past decade, with continuous advancements and expanding applications. To better understand the acceptability of this technology, we report the long-term experiences of health care providers and frontline worker participants with iris scanning as an identification tool in the EBL2007 Ebola vaccine trial conducted in the Democratic Republic of the Congo. ObjectiveThis study aims to document the long-term experiences of using iris scanning for identity verification throughout the vaccine trial. MethodsTwo years after the start of the EBL2007 vaccine trial (February to March 2022), 69 trial participants—including nurses, first aid workers, midwives, and community health workers—were interviewed through focus group discussions. Additionally, 13 in-depth individual interviews were conducted with physicians involved in the trial, iris scan operators, trial staff physicians, and trial participants who declined iris scanning. Qualitative content analysis was used to identify key themes. ResultsInitially, interviewees widely accepted the iris scan and viewed it as a distinctive tool for identifying participants in the EBL2007 vaccine trial. However, over time, perceptions became less favorable. Some participants expressed concerns that their vision had diminished shortly after using the tool and continued to decline until the end of the study. Others reported experiencing perceived vision loss long after the trial had concluded. However, no vision impairment was reported as an adverse event or assessed in the trial as being linked to the iris scan, which uses a previously certified safe infrared light for scanning. ConclusionsOur findings highlight the sustained acceptability and perceived high accuracy of the iris scan tool for uniquely identifying adult participants in a vaccine trial over time. Continued efforts to systematically disseminate and reinforce information about the function and safety of this technology are essential. Clearly presenting iris scanning as a safe procedure could help dispel misconceptions, concerns, and perceived risks among potential users in vaccine trials.

The wildlife reservoir and spillover mechanisms of Ebola virus remain elusive despite extensive research efforts in endemic areas. This study employed a One Health approach to examine the virus' circulation in wildlife and the associated human exposure risks in the Tshuapa province of the Democratic Republic of the Congo. We screened 1049 samples from 919 animals, predominantly small mammals, collected in 2021, and 380 samples from inhabitants of Inkanamongo village, the site of an Ebola virus disease outbreak in 2014. These samples were screened for evidence of current (RNA) or past (IgG antibodies) Ebola virus infections. We also conducted interviews with 167 individuals in the surrounding districts to assess their interactions with wildlife. While no Ebola virus RNA was detected in the wildlife samples, anti-orthoebolavirus IgG antibodies were found in 13 bats and 38 rodents. Among the human participants, 120 individuals had IgG antibodies against at least 1 orthoebolavirus antigen, with 12 showing seropositivity for 2 antigens of the same orthoebolavirus, despite not having a prior Ebola disease diagnosis. Furthermore, the majority of respondents reported frequent visits to the forest to hunt a variety of wild animals, particularly ungulates and rodents, which could account for occasional viral spillovers. The absence of active Ebola virus circulation in wildlife may reflect seasonal patterns in reservoir ecology, as those observed in bats. Similarly, seasonal human activities, such as hunting and foraging, may result in periodic exposure risks. These findings highlight the importance of continuous, multidisciplinary surveillance to monitor changes in seasonal spillover risks.

Background: The long-term retention of information disclosed during the informed consent in clinical trials lasting over a year cannot be guaranteed for all volunteers. This study aimed to assess the level of participants' retention and understanding of the trial information after two years of participation in a vaccine trial. Methods: In total, 699 health care providers (HCPs) and frontline workers were enrolled in the EBL2007 vaccine trial conducted between February 2019 and September 2022 in the Health District of Boende, Democratic Republic of the Congo (DRC). Individual scores obtained from a questionnaire (test of understanding, TOU), specifically designed to assess the understanding of the consent at baseline, were collected before the clinical trial started and at one-year and two-year intervals. Results: TOU scores were high in the beginning of the trial (median TOU = 10/10), but significantly decreased in both the first and second years following (median TOU = 8/10 in year 1 and median TOU = 9/10 in year 2, pvalue < 0.0001). The decrease in scores was significantly higher among individuals with occupations requiring shorter education such as midwives (median TOU = 7/10 in year 1 and 8/10 in year 2, pvalue = 0.025). Furthermore, older participants exhibited poorer retention of information compared to younger individuals (median TOU = 8/10 vs 9/10, p-value = 0.007). Conclusion: We observed a significant decline in the informational knowledge of informed consent, specifically in terms of basic knowledge on the study vaccine and trial procedures. As participant safety and understanding is a paramount ethical concern for researchers, it is crucial for participants to fully comprehend the study's objectives and potential risks. Therefore, our findings suggest the need for clinical researchers to re-explain participants to optimize the protection of their rights and wellbeing during the research.

BACKGROUND In response to recent Ebola epidemics, vaccine development against the Zaire ebolavirus (EBOV) has been fast-tracked in the past decade. Health care providers and frontliners working in Ebola-endemic areas are at high risk of contracting and spreading the virus. METHODS This study assessed the safety and immunogenicity of the 2-dose heterologous Ad26.ZEBOV, MVA-BN-Filo vaccine regimen (administered at a 56-day interval) among 699 health care providers and frontliners taking part in a phase 2, monocentric, randomized vaccine trial in Boende, the Democratic Republic of Congo. The first participant was enrolled and vaccinated on 18 December 2019. Serious adverse events were collected up to 6 months after the last received dose. The EBOV glycoprotein FANG ELISA (Filovirus Animal Nonclinical Group enzyme-linked immunosorbent assay) was used to measure the immunoglobulin G-binding antibody response to the EBOV glycoprotein. RESULTS The vaccine regimen was well tolerated with no vaccine-related serious adverse events reported. Twenty-one days after the second dose, an EBOV glycoprotein-specific binding antibody response was observed in 95.2% of participants. CONCLUSIONS The 2-dose vaccine regimen was well tolerated and led to a high antibody response among fully vaccinated health care providers and frontliners in Boende.

This study explored the experiences of healthcare providers (HCPs) and frontline workers who were involved in an Ebola vaccine trial in the Democratic Republic of the Congo. The researchers interviewed a total of 99 participants (HCPs and frontline workers) living and working in the Boende health district during the period of the study, from February to March 2022. These individuals included a mix of trial participants and non-trial participants (staff of the trial, local health authorities, and head nurses of health centers). In-depth individual interviews, as well as focus group discussions (FGDs), were used to understand interviewees’ experiences and perceptions. The data were analyzed to identify the main themes. The findings unveiled a multitude of positive experiences among interviewees/FGD participants. The commitment of the trial investigators to improve the study site and to equip the volunteers with necessary skills and knowledge greatly contributed to a positive trial experience. However, some interviewees felt that the reimbursement for time and travel expenses during their trial visits was insufficient in comparison with their expectations. Additionally, there were expressions of worry about the frequency of blood draws during scheduled trial visits. Our findings emphasize the critical importance of addressing and continuously considering the perspectives and concerns of trial participants before designing and implementing vaccine trials. By actively incorporating their inputs, researchers can mitigate concerns and tailor communication strategies, potentially enhancing the overall success and impact of the vaccine trial.

BACKGROUND:Health-care providers and front-line workers are at risk of contracting Ebola virus disease during an Ebola virus outbreak and consequently of becoming drivers of the disease. We aimed to assess the long-term immunogenicity of the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen and the safety of and immune memory response to an Ad26.ZEBOV booster vaccination at 1 year or 2 years after the first dose in this at-risk population. METHODS:This open-label, single-centre, randomised, phase 2 trial was conducted at one study site within a hospital in Boende, Democratic Republic of the Congo. Adult health-care providers and front-line workers, excluding those with a known history of Ebola virus disease, were vaccinated with a two-dose heterologous regimen administered at a 56-day interval via a 0·5 mL intramuscular injection in the deltoid muscle, comprising Ad26.ZEBOV as the first dose and MVA-BN-Filo as the second dose. After the initial vaccination on day 1, participants were randomly assigned (1:1) via randomisation envelopes, opened in a sequential order, to receive an Ad26.ZEBOV booster vaccination at 1 year (group 1) or 2 years (group 2) after the first dose. We present the secondary and exploratory objectives of the trial-results of the primary objective have been published elsewhere. We measured immunogenicity at six timepoints per group as geometric mean concentrations (GMCs) of Ebola virus glycoprotein-specific IgG binding antibodies, using the Filovirus Animal Non-Clinical Group ELISA. We assessed serious adverse events occurring up to 6 months after the last dose and local and systemic solicited and unsolicited adverse events reported for 7 days after the booster vaccination. Antibody responses were analysed per protocol, serious adverse events per full analysis set (FAS), and adverse events for all boosted FAS participants. This trial is registered as completed on ClinicalTrials.gov (NCT04186000). FINDINGS:Between Dec 18, 2019, and Feb 8, 2020, 699 health-care providers and front-line workers were enrolled and 698 were randomly assigned (350 to group 1 and 348 to group 2 [FAS]); 534 (77%) participants were male and 164 (23%) were female. 319 in group 1 and 317 in group 2 received the booster. 29 (8%) in group 1 and 26 (7%) in group 2 did not complete the study, mostly due to loss to follow-up or moving out of the study area. In both groups, injection-site pain or tenderness (87 [27%] of 319 group 1 participants vs 90 [28%] of 317 group 2 participants) and headache (91 [29%] vs 93 [29%]) were the most common solicited adverse events related to the investigational product. One participant (in group 2) had a related serious adverse event after booster vaccination (fever of ≥40·0°C). Before booster vaccination, Ebola virus glycoprotein-specific IgG binding antibody GMCs were 279·9 ELISA units (EU) per mL (95% CI 250·6-312·7) in 314 group 1 participants (1 year after first dose) and 274·6 EU/mL (242·1-311·5) in 310 group 2 participants (2 years after first dose). These values were 5·2 times higher in group 1 and 4·9 times higher in group 2 than before vaccination on day 1. 7 days after booster vaccination, these values increased to 10 781·6 EU/mL (9354·4-12 426·4) for group 1 and 10 746·9 EU/mL (9208·7-12 542·0) for group 2, which were approximately 39 times higher than before booster vaccination in both groups. 1 year after booster vaccination in 299 group 1 participants, a GMC that was 7·6-times higher than before booster vaccination was still observed (2133·1 EU/mL [1827·7-2489·7]). INTERPRETATION:Overall, the vaccine regimen and booster dose were well tolerated. A similar and robust humoral immune response was observed for participants boosted 1 year and 2 years after the first dose, supporting the use of the regimen and flexibility of booster dose administration for prophylactic vaccination in at-risk populations. FUNDING:Innovative Medicines Initiative 2 Joint Undertaking and Coalition for Epidemic Preparedness Innovations.

Introduction Clear guidelines to implement ancillary care (AC) in clinical trials conducted in resource-constrained settings are lacking. Here, we evaluate an AC policy developed for a vaccine trial in the Democratic Republic of the Congo and formulate policy recommendations. Methods To evaluate the AC policy, we performed a longitudinal cohort study, nested in an open-label, single-centre, randomised Ebola vaccine trial conducted among healthcare personnel. Participants' demographic information, residence distance to the study site and details on the financial and/or medical support provided for any (serious) adverse events ((S)AE) were combined and analysed. To assess the feasibility of the AC policy, an expenditure analysis of the costs related to AC support outcomes was performed. Results Enrolment in this evaluation study started on 29 November 2021. The study lasted 11 months and included 655 participants from the Ebola vaccine trial. In total, 393 participants used the AC policy, mostly for AE management (703 AE and 94 SAE) via medication provided by the study pharmacy (75.3%). Men had a 35.2% (95% CI 4.0% to 56.6%) lower likelihood of reporting AE compared with women. Likewise, this was 32.3% lower (95% CI 5.8% to 51.4%) for facility-based compared with community-based healthcare providers. The daily AE reporting was 78.8% lower during the passive vs the active trial stage, and 97.4% lower during unscheduled vs scheduled visits (p<0.001). Participants living further than 10 km from the trial site more frequently reported the travel distance as a reason for not using the policy (p<0.04). In practice, only 1.1% of the operational trial budget was used for AC policy support. Conclusion The trial design, study population and local health system impacted the use of the AC policy. Nonetheless, the AC policy implementation in this remote and resource-constrained setting was feasible, had negligible budgetary implications and contributed to participants' healthcare options and well-being.

Iris scanning, as a means of human biometric recognition, has been increasingly deployed over the last decade and continues to improve and expand. To better understand the acceptability of this technology, we report the long-term experiences of healthcare provider (HCP) and frontline worker participants with iris scanning as an identification tool in an Ebola vaccine (EBL2007 vaccine trial) trial conducted in the Democratic Republic of the Congo (DRC). To document the long-term experiences with iris scanning for identity verification throughout this vaccine trial. Two years after the start of the EBL2007 vaccine trial (February-March 2022), 69 trial participants, comprising of nurses, First Aid Workers, Midwives, and Community Health Workers, were interviewed using focus group discussions. . Thirteen individual in-depth interviews were conducted with physicians partaking in the trial, iris scan operators, trial staff physicians, and trial participants who declined iris scanning. Qualitative content analysis was utilized to identify significant themes. Interviewees had initially widely accepted the iris scan and viewed this tool as a distinctive means to identify individuals participating in the EBL2007 vaccine trial. However, over time, this perception shifted to become less favourable. Some voiced concern that their vision diminished soon after using the tool, and that this continued until the end of the study. Others reported that the perception of diminished vision started long after the end of the clinical trial. However, no vision impairment had been reported as an adverse event or assessed in the trial as being associated with the use of the iris scan, which employs a previously certified safe infrared light for iris scanning. Our findings underline the continuous acceptability and perceived high accuracy of the iris scan tool for unique recognition of adult participants in a vaccine trial over time. Continued endeavors to systematically disseminate and reiterate information concerning the functioning and safety of this innovative technology to potential users are imperative. Precise depiction of iris scanning as a harmless procedure could dispel misunderstandings, concerns, and perceived risks among its potential users in a vaccine trial.

In this paper, we discuss challenges associated with implementing a policy for Ancillary Care (AC) for related and unrelated (serious) adverse events during an Ebola vaccine trial conducted in a remote area of the Democratic Republic of the Congo. Conducting clinical trials in resourceconstrained settings can raise context-related challenges that have implications for study participants’ health and wellbeing. During the Ebola vaccine study, three participants were injured in road traffic accidents, but there were unexpected difficulties when trying to apply the AC policy. First, because of the nature of the adverse events, the insurer refused to cover the costs. Second, the AC policy did not address treatments by traditional medicine, even though traditional medicines are frequently used and highly trusted in the study community. This highlighted a contrast between the researchers’ well-intentioned AC approach and the participants’ legitimate preferences. The way in which researchers should address their responsibility to provide AC is not straightforward; it requires contextualization. Our experience highlights the importance of involving community representatives and the local ethics committee to ensure development of an AC policy that is culturally and ethically appropriate. Additionally, the insurance contract should clearly stipulate which adverse events are linked to the trial participation, and thus eligible for coverage, to avoid controversies when claims are made.

Conducting a vaccine trial in a low- and middle-income country (LMIC) can present unique challenges and lessons learned. This Ebola vaccine trial, enrolling 699 healthcare providers and frontliners and jointly set up by the University of Antwerp (Sponsor) and the University of Kinshasa (Principal Investigator (PI)), was conducted in Boende, a remote city in the Democratic Republic of the Congo (DRC), between December 2019 and October 2022 (ClinicalTrials.gov: NCT04186000). While being bound by strict ICH-GCP and international funder regulations, this trial, exemplary for being a public-private partnership, required collaboration between several international stakeholders (e.g., two universities, a pharmaceutical company, and a clinical research organization), local communities and government agencies. Here we address several logistical and administrative challenges, cultural differences, language barriers and regulatory, political, and ethical considerations over the trial's 2.5year duration, while tailoring and adapting the study to the specific local context. Lessons learned include the importance of clear communication with participants in all phases of the study, but also within the study team and among different stakeholders. Challenges, mitigations, and lessons learned are presented in nine categories (e.g., safety management; trial documentation, tools, and materials; communication, staff training and community engagement/sensitization; financial and administrative hurdles; and more). Ultimately, to reach the successful end of the vaccine trial in this remote Ebola endemic area in the DRC, careful planning, collaboration, and great flexibility and adaptability was often required from all involved partners. Despite the encountered challenges, the vaccine trial discussed in this paper was able to obtain high participant retention rates (i.e., 92% of participants completed the study). We hope that other international teams aspiring to conduct similar trials in remote areas of LMICs can learn from the way our challenges were addressed, mitigations developed, and lessons were learned.

INTRODUCTION:A serosurvey among health care providers (HCPs) and frontliners of an area previously affected by Ebola virus disease (EVD) in the Democratic Republic of the Congo (DRC) was conducted to assess the seroreactivity to Ebola virus antigens.METHODS:Serum samples were collected in a cohort of HCPs and frontliners (n = 698) participants in the EBL2007 vaccine trial (December 2019 to October 2022). Specimens seroreactive for EBOV were confirmed using either the Filovirus Animal Nonclinical Group (FANG) ELISA or a Luminex multiplex assay.RESULTS:The seroreactivity to at least two EBOV-Mayinga (m) antigens was found in 10 (1.4%: 95% CI, 0.7-2.6) samples for GP-EBOV-m + VP40-EBOV-m, and 2 (0.3%: 95% CI, 0.0-1.0) samples for VP40-EBOV-m + NP-EBOV-m using the Luminex assay. Seroreactivity to GP-EBOV-Kikwit (k) was observed in 59 (8.5%: 95%CI, 6.5-10.9) samples using FANG ELISA.CONCLUSION:In contrast to previous serosurveys, a low seroprevalence was found in the HCP and frontline population participating in the EBL2007 Ebola vaccine trial in Boende, DRC. This underscores the high need for standardized antibody assays and cutoffs in EBOV serosurveys to avoid the broad range of reported EBOV seroprevalence rates in EBOV endemic areas.