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BACKGROUND: Pertussis vaccination in pregnancy has been introduced in an increasing number of countries to better protect infants against the disease in their first weeks of life. The optimal timing of pertussis vaccination in pregnancy is however still under debate. METHODS: We systematically reviewed published literature on safety, immunogenicity and effectiveness of pertussis vaccination in pregnancy related to timing of vaccination. The search was conducted using PubMed, MEDLINE and Web of Science and yielded 1623 articles, thereof 777 duplicates. Screening resulted in the inclusion of 45 publications reporting on safety (n = 11), immunogenicity (n = 26) and/or effectiveness (n = 9). We also mapped pertussis recommendations in pregnancy by government institutions globally according to the recommended timing of vaccination. RESULTS: Overall, the selected publications did not indicate increased safety concerns associated with timing of pertussis vaccination in pregnancy. Immunogenicity studies often suggested optimal protection at birth after early third trimester vaccination. Few studies investigated qualitative antibody characteristics, and none investigated antibody titers in breastmilk or cellular-mediated immunity related to timing of vaccination. Effectiveness studies showed decreased vaccine effectiveness of late third trimester pertussis vaccination compared to vaccination earlier in pregnancy. Worldwide, a general recommendation for pertussis vaccination in pregnancy was found for 58 countries, with as many as 22 different recommended timings registered. CONCLUSION: The timing of pertussis vaccination in pregnancy seems to impact immunogenicity and vaccine effectiveness, with optimal immune responses at birth suggested following early third trimester vaccination and reduced vaccine effectiveness of late third trimester pertussis vaccination suggested compared to vaccination earlier in pregnancy. However, inconsistent and lacking data are reflected in the divergent national recommendations for pertussis vaccination in pregnancy worldwide. SUMMARY: Pertussis vaccination in pregnancy aims to protect infants in their first weeks of life. Our review suggests that immunogenicity and vaccine effectiveness are impacted by the timing of vaccination in pregnancy. National recommendations for pertussis vaccination in pregnancy vary widely worldwide.
Subject(s)
Pertussis Vaccine , Vaccination , Whooping Cough , Humans , Pregnancy , Female , Whooping Cough/prevention & control , Whooping Cough/immunology , Pertussis Vaccine/administration & dosage , Pertussis Vaccine/immunology , Vaccination/methods , Immunization Schedule , Vaccine Efficacy , Time FactorsABSTRACT
New COVID-19 strains and waning vaccine effectiveness prompted initiatives for booster vaccination. In Belgium, healthcare providers (HCPs) received a second booster in July 2022, with eligible individuals receiving a third in autumn. Primary HCPs (PHCPs) play a crucial role in healthcare organization and patient communication. This study, conducted in February-March 2023, surveyed 1900 Belgian PHCPs to assess their views on periodic COVID-19 boosters for themselves and their patients. The survey included questions on sociodemographic information, willingness to receive periodic COVID-19 boosters, reasons for acceptance or refusal, confidence in vaccine safety and efficacy, and views on booster recommendations. Overall, 86% of participants were willing to receive periodic COVID-19 boosters, motivated by self-protection, patient well-being, and the uninterrupted delivery of healthcare services. Factors influencing booster refusal included not being a general practitioner (GP) or GP trainee, working in Wallonia or Brussels, and lacking vaccine confidence. Although 243 participants would not take boosters periodically, only 74 would not recommend it. Regarding administration, 59% supported pharmacist involvement in COVID-19 vaccination. Further qualitative analysis of 290 PHCPs' responses revealed varying recommendations, including specific roles like nurses, organizational structures, and collaborative approaches. This study highlights the need to address vaccine confidence, regional disparities, and PHCP roles in booster implementation.
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BACKGROUND: WHO postulates the application of adaptive design features in the global clinical trial ecosystem. However, the adaptive platform trial (APT) methodology has not been widely adopted in clinical research on vaccines. METHODS: The VACCELERATE Consortium organized a two-day workshop to discuss the applicability of APT methodology in vaccine trials under non-pandemic as well as pandemic conditions. Core aspects of the discussions are summarized in this article. RESULTS: An "ever-warm" APT appears ideally suited to improve efficiency and speed of vaccine research. Continuous learning based on accumulating APT trial data allows for pre-planned adaptations during its course. Given the relative design complexity, alignment of all stakeholders at all stages of an APT is central. Vaccine trial modelling is crucial, both before and in a pandemic emergency. Various inferential paradigms are possible (frequentist, likelihood, or Bayesian). The focus in the interpandemic interval may be on research gaps left by industry trials. For activation in emergency, template Disease X protocols of syndromal design for pathogens yet unknown need to be stockpiled and updated regularly. Governance of a vaccine APT should be fully integrated into supranational pandemic response mechanisms. DISCUSSION: A broad range of adaptive features can be applied in platform trials on vaccines. Faster knowledge generation comes with increased complexity of trial design. Design complexity should not preclude simple execution at trial sites. Continuously generated evidence represents a return on investment that will garner societal support for sustainable funding. Adaptive design features will naturally find their way into platform trials on vaccines.
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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.
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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.
Subject(s)
Ebola Vaccines , Humans , Male , Female , Ebola Vaccines/economics , Adult , Democratic Republic of the Congo , Longitudinal Studies , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/economics , Health Policy , Middle Aged , Health PersonnelABSTRACT
BACKGROUND: The VACCELERATE Pan-European Scientific network aims to strengthen the foundation of vaccine trial research across Europe by following the principles of equity, inclusion, and diversity. The VACCELERATE Volunteer Registry network provides access to vaccine trial sites across the European region and supports a sustainable volunteer platform for identifying potential participants for forthcoming vaccine clinical research. OBJECTIVE: The aim of this study was to approach members of patient advocacy groups (PAGs) across Europe to assess their willingness to register for the VACCELERATE Volunteer Registry and their perspectives related to participating in vaccine trials. METHODS: In an effort to understand how to increase recruitment for the VACCELERATE Volunteer Registry, a standardized survey was developed in English and translated into 8 different languages (Dutch, English, French, German, Greek, Italian, Spanish, and Swedish) by the respective National Coordinator team. The online, anonymous survey was circulated, from March 2022 to May 2022, to PAGs across 10 European countries (Belgium, Cyprus, Denmark, France, Germany, Greece, Ireland, Italy, Spain, and Sweden) to share with their members. The questionnaire constituted of multiple choice and open-ended questions evaluating information regarding participants' perceptions on participating in vaccine trials and their willingness to become involved in the VACCELERATE Volunteer Registry. RESULTS: In total, 520 responses were collected and analyzed. The PAG members reported that the principal criteria influencing their decision to participate in clinical trials overall are (1) the risks involved, (2) the benefits that will be gained from their potential participation, and (3) the quality and quantity of information provided regarding the trial. The survey revealed that, out of the 520 respondents, 133 individuals across all age groups were "positive" toward registering in the VACCELERATE Volunteer Registry, with an additional 47 individuals reporting being "very positive." Respondents from Northern European countries were 1.725 (95% CI 1.206-2.468) times more likely to be willing to participate in the VACCELERATE Volunteer Registry than respondents from Southern European countries. CONCLUSIONS: Factors discouraging participants from joining vaccine trial registries or clinical trials primarily include concerns of the safety of novel vaccines and a lack of trust in those involved in vaccine development. These outcomes aid in identifying issues and setbacks in present registries, providing the VACCELERATE network with feedback on how to potentially increase participation and enrollment in trials across Europe. Development of European health communication strategies among diverse public communities, especially via PAGs, is the key for increasing patients' willingness to participate in clinical studies.
Subject(s)
Patient Advocacy , Vaccines , Humans , Europe , France , Germany , Clinical Trials as TopicABSTRACT
Background and aims: In low endemic countries, screening for hepatitis B surface antigen (HBsAg) in migrants is cost-effective in reducing the disease burden of hepatitis B virus (HBV) infections, but linkage to care (LTC) remains a challenge. This study aims to guide future screening initiatives, with 3 objectives: 1. to compare LTC between different ethnic groups screened for HBsAg with point-of-care testing (POCT) in an outreach setting; 2. to estimate the proportion of HBsAg seropositivity for ethnic minorities; and 3. to investigate the association between seropositivity and HBV risk factors. Methods: Opportunistic outreach screenings using finger prick HBsAg tests were performed at civic integration programmes between 11/2017 and 09/2022. If an individual tested positive, an appointment was given immediately at the outpatient hepatology clinic for follow-up and confirmation of HBsAg positivity in blood. Dedicated personnel contacted these individuals to motivate them for further LTC, which was defined as being assessed by a hepatologist, a blood test and an abdominal ultrasound. Results: A total of 677 people from different ethnicities (Asian, Middle Eastern and African) were serologically screened using POCT. The observed positivity for HBsAg was 3.4 % (95% CI 2.17-5.05, 23/677). Apart from ethnicity and male sex, none of the surveyed HBV risk factors were associated with HBsAg seropositivity. All HBsAg positive individuals were linked to care and assessed by a hepatologist, despite the COVID-19 pandemic increase in time to follow-up of 82 days (95% CI 51-112 days) vs. 24 days (95% CI 5-43 days, p = 0.008)).Among HBV-infected patients, 31.8% (7/22), 100 % (22/22) and 26.1% (6/23) met the criteria for treatment indication, intrafamilial transmission risk and need for hepatocellular carcinoma surveillance, respectively. Conclusion: The proportion of HBsAg seropositivity in ethnic minorities was 3.4%. POCT and commitment of dedicated personnel can overcome previously identified barriers resulting in a 100% LTC.
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The role of T cell receptor (TCR) diversity in infectious disease susceptibility is not well understood. We use a systems immunology approach on three cohorts of herpes zoster (HZ) patients and controls to investigate whether TCR diversity against varicella-zoster virus (VZV) influences the risk of HZ. We show that CD4+ T cell TCR diversity against VZV glycoprotein E (gE) and immediate early 63 protein (IE63) after 1-week culture is more restricted in HZ patients. Single-cell RNA and TCR sequencing of VZV-specific T cells shows that T cell activation pathways are significantly decreased after stimulation with VZV peptides in convalescent HZ patients. TCR clustering indicates that TCRs from HZ patients co-cluster more often together than TCRs from controls. Collectively, our results suggest that not only lower VZV-specific TCR diversity but also reduced functional TCR affinity for VZV-specific proteins in HZ patients leads to lower T cell activation and consequently affects the susceptibility for viral reactivation.
Subject(s)
Herpes Zoster , Herpesvirus 3, Human , Lymphocyte Activation , Receptors, Antigen, T-Cell , Humans , Herpes Zoster/immunology , Herpes Zoster/virology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/immunology , Lymphocyte Activation/immunology , Herpesvirus 3, Human/immunology , Female , Middle Aged , Male , CD4-Positive T-Lymphocytes/immunology , Aged , Adult , Epitopes, T-Lymphocyte/immunologyABSTRACT
Healthcare providers (HCP) are seen by the public as the most trustworthy source of information about vaccination. While HCPs could be a valuable partner to increase vaccine confidence in general, it is not clear whether they feel confident themselves to address questions concerning vaccination. In the context of the EU Joint Action on Vaccination (EU-JAV), the Vaccine Training Barometer, an online survey tool, was developed to assess how frequently HCPs receive questions about vaccination, how confident they feel to answer these questions, and to what extent they are willing to follow extra training. After a pilot test in Flanders, Belgium, the Barometer was launched and completed by 833 HCPs in Flanders and 291 HCPs in the Spanish regions of Catalonia, Navarre and Valencian Community from November 2020 until January 2021, during the COVID-19 pandemic, just before and during the start of the first COVID-19 vaccination campaigns. In both countries, HCPs frequently received questions about vaccination (mostly on a daily or weekly basis), and about two thirds of them indicated that the frequency of questions had increased during the three months prior to completing the survey. Most questions were about the side effects and safety of vaccines. In both countries, a considerable proportion of HCPs did not feel confident to answer vaccine-related questions (31.5% felt confident in Flanders, 21.6% in Spain). A large proportion of HCPs received questions in the last three months before the survey that they could not answer (52.4% of respondents in Flemish sample, 41.5% in Spanish sample). Only 11.4% (Flanders) and 11.3% (Spain) of the respondents felt they gained sufficient knowledge through their standard education to be able to answer questions about vaccination. Almost all respondents were willing to follow extra training on vaccination (Flanders: 95.4%, Spain: 96.6%). The Vaccine Training Barometer is thus a useful tool to monitor HCPs' confidence to answer questions about vaccination and to capture their training needs.
Subject(s)
COVID-19 Vaccines , Vaccines , Humans , Pandemics , Health Knowledge, Attitudes, Practice , Vaccines/adverse effects , Vaccination , Health PersonnelABSTRACT
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 10â781·6 EU/mL (9354·4-12â426·4) for group 1 and 10â746·9 EU/mL (9208·7-12â542·0) 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.
Subject(s)
Antibodies, Viral , Ebola Vaccines , Ebolavirus , Health Personnel , Hemorrhagic Fever, Ebola , Immunization, Secondary , Humans , Democratic Republic of the Congo , Hemorrhagic Fever, Ebola/prevention & control , Hemorrhagic Fever, Ebola/immunology , Ebola Vaccines/immunology , Ebola Vaccines/administration & dosage , Ebola Vaccines/adverse effects , Male , Adult , Female , Antibodies, Viral/blood , Ebolavirus/immunology , Ebolavirus/genetics , Middle Aged , Young Adult , Vaccination/methodsABSTRACT
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, p-value < 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.
Subject(s)
Ebola Vaccines , Hemorrhagic Fever, Ebola , Humans , Democratic Republic of the Congo , Ebola Vaccines/adverse effects , Health Personnel , Hemorrhagic Fever, Ebola/prevention & control , Informed Consent , Clinical Trials as TopicABSTRACT
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.
Subject(s)
Ebola Vaccines , Ebolavirus , Hemorrhagic Fever, Ebola , Smallpox Vaccine , Animals , Humans , Democratic Republic of the Congo , Antibodies, Viral , Glycoproteins , Immunogenicity, Vaccine , Vaccines, AttenuatedABSTRACT
Infection with hepatitis D virus leads to liver disease and cancer most rapidly of all hepatitis viruses. However, knowledge about hepatitis D remains poor and the burden and impact are underestimated, even though some 12-15 million people mainly in low- and middle-income countries may be affected. Its epidemiology is changing, with increasing migration leading to increased risks of infection and disease. A recent Viral Hepatitis Prevention Board meeting reviewed the current epidemiological status, improvements in diagnostic testing, advances in the development of novel antiviral agents in phase III trials and the need for a greater public health response, such as new guidelines and recommended testing of all people newly identified as infected with hepatitis B virus for hepatitis D virus infection. It identified issues and needs for attention with regard to prevention, diagnosis and treatment.
Subject(s)
Hepatitis D , Public Health , Humans , Hepatitis D/epidemiology , Antiviral Agents/therapeutic use , Hepatitis Delta Virus , Hepatitis B virusABSTRACT
T-cell-based diagnostic tools identify pathogen exposure but lack differentiation between recent and historical exposures in acute infectious diseases. Here, T-cell receptor (TCR) RNA sequencing was performed on HLA-DR+/CD38+CD8+ T-cell subsets of hospitalized coronavirus disease 2019 (COVID-19) patients (n = 30) and healthy controls (n = 30; 10 of whom had previously been exposed to severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). CDR3α and CDR3ß TCR regions were clustered separately before epitope specificity annotation using a database of SARS-CoV-2-associated CDR3α and CDR3ß sequences corresponding to >1000 SARS-CoV-2 epitopes. The depth of the SARS-CoV-2-associated CDR3α/ß sequences differentiated COVID-19 patients from the healthy controls with a receiver operating characteristic area under the curve of 0.84 ± 0.10. Hence, annotating TCR sequences of activated CD8+ T cells can be used to diagnose an acute viral infection and discriminate it from historical exposure. In essence, this work presents a new paradigm for applying the T-cell repertoire to accomplish TCR-based diagnostics.
Subject(s)
CD8-Positive T-Lymphocytes , COVID-19 , Humans , Receptors, Antigen, T-Cell/genetics , COVID-19/diagnosis , SARS-CoV-2 , T-Lymphocyte Subsets , Epitopes , Epitopes, T-Lymphocyte , COVID-19 TestingABSTRACT
In February 2023, a meeting about correlates of protection (CoPs) against COVID-19 was organized by the International Alliance for Biological Standardization, the European Plotkin Institute for Vaccinology, and Vaccinopolis. The meeting aimed at reviewing the evidence, drawing conclusions, and identifying knowledge gaps. Collection of evidence is not straightforward. Neutralizing antibodies correlate with protection and are used for immunobridging studies within and between vaccine platforms for approval of new COVID-19 vaccines. In preparation for the next pandemic, it is vital that rapidly authorized initial vaccines are available to perform immunobridging studies very early. Additional components of the immune response likely contribute to protection against symptomatic infection. Current evidence is strongest for T lymphocytes and binding antibodies. Further studies are needed to consolidate this evidence and define their potential role in the evaluation of vaccines. For evaluation of mucosal vaccines, identifying CoPs against infection and transmission is key; further research is needed to identify and standardize methods suitable for clinical studies. CoPs for broadly protective beta-coronavirus vaccines remain a critical area of research. The knowledge, expertise, and capacity exist to conduct clinical studies using different designs in different populations to discover and validate CoPs, facilitating and accelerating evaluation of novel vaccines/vaccination platforms.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , Antibodies, Neutralizing , Pandemics/prevention & control , Vaccination , Antibodies, ViralABSTRACT
Underserved and hard-to-reach population groups are under-represented in vaccine trials. Thus, we aimed to identify the challenges of vaccine trial participation of these groups in member countries of the VACCELERATE network. Seventeen National Coordinators (NC), each representing their respective country (15 European countries, Israel, and Turkey), completed an online survey. From 15 eligible groups, those that were more frequently declared underserved/hard-to-reach in vaccine research were ethnic minorities (76.5%), persons experiencing homelessness (70.6%), illegal workers and refugees (64.7%, each). When prioritization for education on vaccine trials was considered, ethnic groups, migrants, and immigrants (5/17, 29.4%) were the groups most frequently identified by the NC as top targets. The most prominent barriers in vaccine trial participation affecting all groups were low levels of health literacy, reluctance to participate in trials due to engagement level, and low levels of trust in vaccines/vaccinations. This study highlighted population groups considered underserved/hard-to-reach in countries contained within the European region, and the respective barriers these groups face when participating in clinical studies. Our findings aid with the design of tailored interventions (within-and across-countries of the European region) and with the development of strategies to overcome major barriers in phase 2 and phase 3 vaccine trial participation.
ABSTRACT
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 2.5-year 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.
Subject(s)
Ebola Vaccines , Hemorrhagic Fever, Ebola , Humans , Communication , Democratic Republic of the Congo/epidemiology , Hemorrhagic Fever, Ebola/epidemiology , Hemorrhagic Fever, Ebola/prevention & control , Universities , Clinical Trials as TopicABSTRACT
Hepatitis A is a vaccine-preventable infection caused by the hepatitis A virus (HAV). Over 150 million new infections of hepatitis A occur annually. HAV causes an acute inflammatory reaction in the liver that usually resolves spontaneously without chronic sequelae. However, up to 20% of patients experience a prolonged or relapsed course and <1% experience acute liver failure. Host factors, such as immunological status, age, pregnancy and underlying hepatic diseases, can affect the severity of disease. Anti-HAV IgG antibodies produced in response to HAV infection persist for life and protect against re-infection; vaccine-induced antibodies against hepatitis A confer long-term protection. The WHO recommends vaccination for individuals at higher risk of infection and/or severe disease in countries with very low and low hepatitis A virus endemicity, and universal childhood vaccination in intermediate endemicity countries. To date, >25 countries worldwide have implemented such programmes, resulting in a reduction in the incidence of HAV infection. Improving hygiene and sanitation, rapid identification of outbreaks and fast and accurate intervention in outbreak control are essential to reducing HAV transmission.
ABSTRACT
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.