Ebola Vaccine Research Articles

Development and characterization of a Zaire Ebola (ZEBOV) specific IgM ELISA

Immunoglobulin M (IgM) is the first antibody induced after the onset of an adaptive immune response against a pathogen or vaccine. Serological assays play a central role in evaluating these adaptive immunological responses. Such assays are not only crucial for the assessment of vaccine immunogenicity, but also inform on exposure to pathogens and cross-reactivity with other viruses. To date, there is no ELISA-based assay available that measures IgM responses against Zaire Ebola virus (ZEBOV). To address this critical need, our laboratory has developed a novel immunoassay capable of detecting total IgM against ZEBOV glycoprotein in serum samples from individuals exposed to the antigen through infection or vaccination. Here, we describe a sensitive, high-throughput, and inexpensive assay that can be performed in any laboratory. The performance criteria of the newly developed ZEBOV glycoprotein-based IgM ELISA were assessed using antisera collected from human patients immunized with the rVSVΔG-ZEBOV-GP vaccine being tested in a phase 1 clinical trial. This assay demonstrates high specificity and sensitivity and will also be a valuable tool in the mission to find immune correlates of protection for a successful Ebola vaccine.

Perceptions and acceptability of an experimental Ebola vaccine among health care workers, frontline staff, and the general public during the 2014–2015 Ebola outbreak in Sierra Leone

IntroductionExperimental Ebola vaccines were introduced during the 2014–2015 Ebola outbreak in West Africa. Planning for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) was underway in late 2014. We examined hypothetical acceptability and perceptions of experimental Ebola vaccines among health care workers (HCWs), frontline workers, and the general public to guide ethical communication of risks and benefits of any experimental Ebola vaccine. MethodsBetween December 2014 and January 2015, we conducted in-depth interviews with public health leaders (N = 31), focus groups with HCWs and frontline workers (N = 20), and focus groups with members of the general public (N = 15) in Western Area Urban, Western Area Rural, Port Loko, Bombali, and Tonkolili districts. Themes were identified using qualitative content analysis. ResultsAcross all participant groups, not knowing the immediate and long-term effects of an experimental Ebola vaccine was the most serious concern. Some respondents feared that experimental vaccines may cause Ebola, lead to death, or result in other adverse events. Among HCWs, not knowing the level of protection provided by experimental Ebola vaccines was another concern. HCWs and frontline workers were motivated to help find a vaccine for Ebola to help end the outbreak. General public participants cited positive experiences with routine childhood immunization in Sierra Leone. DiscussionOur formative assessment prior to STRIVE’s implementation in Sierra Leone helped identify concerns, motivations, and information gaps among potential participants of an experimental Ebola vaccine trial, at the time when an unprecedented outbreak was occurring in the country. The findings from this assessment were incorporated early in the process to guide ethical communication of risks and benefits when discussing informed consent for possible participation in the vaccine trial that was launched later in 2015.

Neutralizing Antibody Titer Test of Ebola Recombinant Protein Vaccine and Gene Vector Vaccine pVR-GP-FC

ObjectiveIn previous studies, we immunized mice with Ebola recombinant protein vaccine and gene vector vaccine. Both stimulated high levels of humoral immunity. In this work, we constructed a pseudovirus containing Ebola membrane proteins to verify whether the two immunization strategies can induce neutralizing antibodies in mice. MethodsA pseudovirus containing an Ebola virus membrane protein based on the HIV-1 viral gene sequence was constructed and evaluated using a known neutralizing antibody. The titer of the neutralizing antibody in the sera of mice immunized with the recombinant protein and the gene vector vaccine was examined using a neutralization test. ResultsEbola pseudovirus was successfully prepared and applied for neutralizing antibody detection. Immunological experiments showed that recombinant protein GP-Fc and gene vaccine pVR-modGP-Fc had good immunogenicity. The titer of the bound antibody in the serum after 8 weeks of immunization in mice was more than 1:105, and the recombinant protein induced greater humoral immunity. The results of the neutralization test based on the Ebola pseudovirus system demonstrated that both vaccines induced production of protective antibodies, while the gene vaccine induced a higher titer of neutralizing antibodies. ConclusionAn Ebola pseudovirus detection system was successfully established and used to evaluate two Ebola vaccines. Both produced good immunogenicity. The findings lay the foundation for the development of new Ebola vaccines and screening for neutralizing monoclonal antibodies.

Ebola vaccines: ready to use for humanitarian health workers?

Ebola vaccines: ready to use for humanitarian health workers?

The World after Ebola: An Overview of Ebola Complications, Vaccine Development, Lessons Learned, Financial Losses, and Disease Preparedness.

The 2014-2016 Ebola outbreak in West Africa was the largest of its kind with 11,000 deaths and approximately 28,637 affected cases. The aim of the study was to analyze the global situation after the Ebola outbreak including Ebola complications, vaccine development, lessons learned, financial losses, and disease preparedness. We searched in PubMed, Google, and Google Scholar by using keywords Ebola virus, Ebola vaccine development and Ebola virus transmission, the world after Ebola, financial losses by Ebola outbreak, and disease preparedness. Ebola virus disease is a complex disorder associated with gastrointestinal, hepatic, renal, respiratory, cardiovascular, and neurological complications. Ebola virus persisted in the semen of male infected patients for 470 to 565 days, and the chances of viral transmission by sexual contacts remained high even after patient recovery. There are several reports of extreme socioneuropsychological disorders in Ebola survivors and Ebola healthcare workers. There is no Food and Drug Administration-approved drug or vaccine for Ebola. Many research groups are working to develop a vaccine against Ebola by using different biotechnology techniques. Some vaccine candidates, including replicating vesicular stomatitis virus and Chimpanzee adenovirus-3, have entered phase III clinical trials and are expected to receive clinical licensing in coming years. The West African Ebola epidemic caused a financial loss of $6 billion in Africa and an additional global economic loss of more than $12 billion. After the Ebola epidemic, four global commissions were established for disease preparedness. A proposition was also forwarded to the World Health Organization for the establishment of the Centre for Emergency Preparedness and Response for the disease management. The devastating Ebola epidemic opened the window for disease preparedness to face any future disease epidemic.

Precarity, clinical labour and graduation from Ebola clinical research in West Africa

ABSTRACTThe provision of gifts and payments for healthy volunteer subjects remains an important topic in global health research ethics. This paper provides empirical insights into theoretical debates by documenting participants' perspectives on an Ebola vaccine trial in West Africa. This trial provided hundreds of Africans with regular payments, food packages and certificates for participation. The researchers conducting the trials considered these socioeconomic provisions to be gifts in accordance with contemporary ethical standards and principles. Trial participants viewed them differently, however, approaching trial participation as a means for training and employment in what was from their perspective a new job market: the post-Ebola expansion of research and health care systems. This paper analyses participation in contemporary research by viewing the context-specific histories of trial participants through the lens of prior interventions, specifically participatory reintegration programmes conducted in Anglophone West Africa to overcome civil war crises. In particular, we argue that participation in the Ebola vaccine trial was inadvertently shaped by the design and outcomes of past reintegration programmes. Our results highlight the need to investigate existing socioeconomic landscapes which surround and indeed permeate clinical research as a prerequisite for understanding the participatory motives of vulnerable participants in West Africa and elsewhere.

Chimpanzee adenoviral vector prime-boost regimen elicits potent immune responses against Ebola virus in mice and rhesus macaques

ABSTRACT In the last few decades, Ebola virus (EBOV) has emerged periodically and infected people in Africa, resulting in an extremely high mortality rate. With no available prophylaxis or cure so far, a highly effective Ebola vaccine is urgently needed. In this study, we developed a novel chimpanzee adenovirus-based prime-boost vaccine by exploiting two recombinant replication-deficient chimpanzee adenoviral vectors, AdC7 and AdC68, which express glycoproteins (GP) of the EBOV strain identified in the 2014 outbreak. Our results indicated that a single immunization using AdC7 or AdC68 could stimulate potent EBOV-specific antibody responses, whereas the AdC7 prime-AdC68 boost regimen induced much stronger and sustained humoral and cellular immune responses in both mice and rhesus monkeys, compared with AdC7 or AdC68 single vaccination or the AdC68 prime-AdC7 boost regimen. This prime-boost vaccine could also protect mice from the simulated infection with EBOV-like particle (EBOVLP) in biosafety level 2 (BSL-2) laboratories, and antibodies from the prime-boost immunized rhesus macaques could passively provide protection against EBOVLP infection. Altogether, our results show that the AdC7 prime-AdC68 boost vaccine is a promising candidate for further development to combat EBOV infections.

In the shadow of tomorrow

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Ebola vaccine is having ‘major impact’ but Congo outbreak may still explode

Ebola vaccine is having ‘major impact’ but Congo outbreak may still explode

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/HypothesisRecruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study. MethodsAn online survey which included participants’ prior experience with clinical trials, motivations to participate (including financial incentives), and demographic information was developed to examine the motivations of healthy participants in two phase 1 clinical vaccine trials conducted at the Canadian Center for Vaccinology in Halifax, Nova Scotia. Participants were invited via email to complete the online survey. Readability and clarity were assessed through pilot testing. ResultsA total of 49 (55.7%) of 88 participants of the two studies completed the survey (22 [55%] of 40 participants from the Ebola vaccine study and 27 [56.3%] of 48 from the adjuvanted influenza vaccine study). Motivations that were most frequently ranked among participants' top three in both trials were (1) wanting to contribute to the health of others, (2) wanting to participate in something important, (3) wanting to contribute to the advancement of science, and (4) wanting to receive an incentive such as money or a tablet. Conclusions/RecommendationsAlthough media attention and financial compensation were more often cited by Ebola vaccine trial participants as a reason to participate, both altruistic and self-interested factors were important motivations for participants in their decision to participate in a phase 1 vaccine clinical trial.

Clinical Trials and Administration of Zika Virus Vaccine in Pregnant Women: Lessons (that Should Have Been) Learned from Excluding Immunization with the Ebola Vaccine during Pregnancy and Lactation.

As evidenced from recent epidemics, both Ebola and Zika virus infection are potentially catastrophic when occurring in pregnant women. Ebola virus causes extremely high rates of mortality in both mothers and infants; Zika virus is a TORCH infection that produces a congenital malformation syndrome and pediatric neurodevelopmental abnormalities. Production of efficacious vaccines has been a public health priority for both infections. Unfortunately, during the clinical trials and subsequent deployment of a vaccine for the Ebola virus, pregnant and lactating women were, and continue to be, excluded from receiving the life-saving vaccine. The most serious consequence of Zika virus infection, congenital Zika syndrome, results from fetal infection during pregnancy. Thus, pregnant women have a major stake in the ongoing development of a vaccine for Zika virus. The exclusion of pregnant women from the development, clinical trials and administration of a potential Zika vaccine unfairly deprives them and their infants of the protection they need against this potentially catastrophic intrauterine infection. When creating policy about these issues, it is important to critically evaluate vaccine safety in pregnancy in the context of the substantial risk of infection for the pregnant woman and her fetus in the absence of immunization.

Establishing China's National Standard for the Recombinant Adenovirus Type 5 Vector-Based Ebola Vaccine (Ad5-EBOV) Virus Titer.

The 2014 Ebola outbreak in West Africa brought great threat to public health worldwide. There was no approved antiviral therapy or vaccine available to control the disease at that time. Several kinds of Ebola vaccines were urgently under development across the world. Among these, the novel recombinant adenovirus type 5 vector-based Ebola vaccine (Ad5-EBOV)-the first Ebola vaccine based on the 2014 Zaire Guinea epidemic strain-was developed in China, and its safety and immunogenicity were demonstrated in China and Sierra Leone. The license to market the drug was approved on October 19, 2017, by the Chinese Food and Drug Administration. In order to standardize the test on the Ad5-EBOV virus titer, China's national standard substance for the virus titer of Ad5-EBOV was established according to the recommendations for the preparation, characterization, and establishment of international and other biological reference standards from the World Health Organization and Chinese Pharmacopoeia (third edition). The standard for the Ad5-EBOV virus titer was prepared with a volume of 0.5 mL per ampoule in lyophilized form. The samples of the standard, designated as A, B, C, D with different aims, were blinded and distributed to five laboratories to be collaboratively calibrated. The virus titer for this standard was determined with the antibody staining method according to the instructions in the Adeno-X™ Rapid Titer Kit. The homogeneity and stability of the standard substance were also satisfied. The virus titer standard value was 8.54 lg infectious units (IFU)/mL, and the 95% confidence interval was between 7.94 lg IFU/mL and 9.14 lg IFU/mL. This standard was approved by the Chinese national committee and is available on the National Institutes for Food and Drug Control Web site ( www.nifdc.org.cn ; lot no. 250019-201501).

EBODAC - Communication strategy and tools for optimizing the impact of Ebola vaccination deployment - H2020

EBODAC - Communication strategy and tools for optimizing the impact of Ebola vaccination deployment - H2020

Citizens, dependents, sons of the soil

The impact of biomedicine and biomedical technologies on identity and sociality has long been the focus of medical anthropology. In this article we revisit these debates in a discussion of how unprecedented encounters with biomedicine during the West African Ebola outbreak have featured in Sierra Leoneans’ understandings of citizenship and belonging, using the case study of an Ebola vaccine trial taking place in Kambia District (EBOVAC Salone). Analysing our ethnographic material in conversation with a historical analysis of notions of belonging and citizenship, we show how participation in a vaccine trial in a moment of crisis allowed people to tell stories about themselves as political subjects and to situate themselves in a conversation about the nature of citizenship that both pre-dates and post-dates the epidemic.

Editorial introductions

Current Opinion in HIV and AIDS was launched in 2006. It is one of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The fields of HIV and AIDS are divided into nine sections that are reviewed once a year. Each section is assigned one or two Section Editors, leading authorities in the area, who identify the most important topics at that time. Here we are pleased to introduce the Journal's Section Editors for this issue. SECTION EDITORS Jean-Daniel LelièvreJean-Daniel LelièvreJean-Daniel Lelièvre is a Professor of Immunology at the University Paris Est Créteil, France. He heads the Department of Clinical Immunology and Infectious Diseases and an INSERM team dedicated to the study of HIV pathophysiology in Hospital Henri Mondor, Créteil, France. He is in the charge of the clinical core of the VRI consortium of research teams dedicated to HIV vaccine research, and of the WP7 (prophylactic vaccine) of the European consortium on HIV research (EHVA). He also heads a lab team devoted to immunological analysis after vaccination and to the development of DC targeting vaccines. Prof. Lelièvre is investigator of several clinical trials in the field of immune-based therapies of HIV infection and HIV vaccine. He is also in charge of the work packages of different European projects on HIV and Ebola vaccines. He is a member of the technical committee of vaccines of the French national agency HAS and the Immunization and Vaccine-Related Implementation Research Advisory Committee (IVIR-AC) of the WHO. Timothy J. HenrichTimothy J. HenrichTimothy J. Henrich is an Associate Professor of Medicine in the Division of Experimental Medicine at the University of California, San Francisco (UCSF), USA. He heads a translational research group focusing on characterizing and targeting persistent HIV reservoirs to achieve long-term HIV remission or functional cure. His laboratory studies the impact of stem cell transplantation and novel immunotherapies on HIV persistence and is engaged in identifying and targeting non-viral markers of HIV infected cells. Dr Henrich is also engaged in projects involving the design and implementation of single-cell bioengineering technologies and PET-based imaging of viral reservoirs.

Development of Ebola Vaccine Candidate by in Silico from Glikoprotein (GP) Gene of Ebola Zaire Virus

Immunoinformatics is the one of bioinformatics divisions. The focus of this division is to design compounds of immune response activists or candidate vaccine in silico or computation. One type of immune response activator compound is a peptide. Peptides are small amounts of amino acid residues. The amount of amino acid residues that can activate the immune response ranges from 9-15 amino acids. Good candidate vaccine quality is shown affinity or strong bond between peptide and MHC (Major Histocompatibility Complex) is indicated by the value of energy of molecule-blocking process through low software. This research is conducted in Data and Process Laboratory of Biology Department, Faculty of Science and Technology, States of Islamic University Sunan Gunung Djati Bandung, in December 2016 until February 2017. The study amis to get candidate vaccine ebola peptide form 9 (nine) amino acid residues. The tool used in this research is the software which made based on the working principle of immune response. The software is SDS Workbench, IEDB-AR, Emboss, and CABSdock. The material used in this research is the sequence information of ebola virus glycoprotein. The results show that the peptides with FLYDRLAST (Fenilanalnin, Leusin, Tyrosine, Aspartic acid, Arginine, Leusin, Alanine, Serin Treonin) are potential candidate for the ebola peptide vaccine because of their high affinity values with MHC I, indicated by molecular-binding energy which is very low ie -1870.69 Kcal / mol.

The Role of The African Vaccine Regulatory Forum (AVAREF) in The Accelerated Clinical Evaluation of Ebola Vaccine Candidates During the Large West Africa Epidemic

In emergency situations, clinical trials of new vaccines and therapies in resource-constrained settings place an additional burden on the limited resources of low and middle-income countries. The clinical trials of vaccines against Ebola Virus Disease (EVD) in Africa presented challenges on how to ensure there was enough capacity for ethics and regulatory reviews and oversight while still allowing for accelerating the clinical evaluations. Using the African Vaccine Regulatory Forum (AVAREF) platform WHO supported African countries to provide ethics and regulatory reviews and oversight, ensuring that these trials were completed in unprecedented shorter timelines than normal, that is, months instead of years. Pathways were defined, external expertise provided and appropriate review models implemented in the countries which hosted these critical studies. This paper discusses the work around the clinical trials, the models of reviews and timelines for clinical trials and highlights the important lessons revealed. More investments are required to monitor safety during clinical trials, strengthen systems for licensure of new products and implement robust post-marketing surveillance, among other components for effective clinical trials before the next pandemic surfaces.

Reliably picking the best endpoint.

Endpoint selection in clinical trials involves a variety of considerations. One important consideration is the sample size required to power a future clinical trial. In this work, we define the sample size ratio, θ, as the ratio of sample sizes required to power a future trial. We consider in detail the setting of continuous endpoints where a Welch's t-statistic is used to analyze the data. We develop an estimator that depends on the squared ratio of estimated standardized treatment effects, and the quadrant on the plane in which they fall. We evaluate bootstrap and profile likelihood methods for construction of confidence intervals. Generalizations to other endpoints and testing of nonnested models are discussed. The methods are applied to analyze two different assays that measure antibody abundance using data from an Ebola vaccine field trial.

Antibody Repertoires to the Same Ebola Vaccine Antigen Are Differentially Affected by Vaccine Vectors

SUMMARYComparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective in guinea pigs but yielded antibody repertoires that differed in proportion targeting key antigenic regions, avidity, neutralizing antibody specificities, and linear epitope preferences. Competition studies with monoclonal antibodies from human survivors revealed that some epitopes in GP targeted for neutralization were vector dependent, while EBOV-neutralizing titers correlated with the response magnitude toward the receptor-binding domain and GP1/GP2 interface epitopes. While an immunogen determines the breadth of antibody response, distinct vaccine vectors can induce qualitatively different responses, affecting protective efficacy. These data suggest that immune correlates of vaccine protection cannot be generalized for all vaccines against the same pathogen, even if they use the exact same immunogen.

Ebola Virus Shed Glycoprotein Triggers Differentiation, Infection, and Death of Monocytes Through Toll-Like Receptor 4 Activation.

A better understanding of the mechanisms used by Ebola virus to disable the host immune system and spread the infection are of great importance for development of new therapeutic strategies. We demonstrate that treatment of monocytic cells with Ebola virus shed glycoprotein (GP) promotes their differentiation resulting in increased infection and cell death. The effects were inhibited by blocking Toll-like receptor 4 pathway. In addition, high levels of shed GP were detected in supernatants of cells treated with Ebola vaccines. This study highlights the role of shed GP in Ebola pathogenesis and also in adverse effects associated with Ebola vaccines.