What Is the Ebola Virus Peer Reviewed Articles
Infectious diseases
Protocol
Effects of vaccines in protecting confronting Ebola virus disease: protocol for a systematic review
Abstract
Introduction Ebola virus disease is one of the most devastating infectious diseases in the globe with upwards to 90% case fatality observed. In that location are at least 13 candidate vaccines developed and beingness tested to prevent the occurrence of the Ebola virus disease. While none of these candidate vaccines has received regulatory approving for use, i candidate vaccine (rVSVΔG-ZEBOV-GP) has been granted access for emergency use. Two other candidate vaccines (GamEvac-Combi and Ad5-EBOV) have been licensed for emergency use in their countries of origin. The objective of this systematic review is to summarise the effects of the Ebola candidate vaccines in humans.
Methods and assay Nosotros volition search for potentially eligible studies, with no linguistic communication or engagement restrictions, in the Cochrane Key Register of Controlled Trials, PubMed, Scopus, the WHO International Clinical Trial Registry Platform, and reference lists of relevant publications. The Cochrane Database of Systematic Reviews (CDSR) and the Database of Abstracts of Reviews of Result (Cartel) volition exist searched for related reviews. Ii review authors volition independently screen search records, assess study eligibility, perform data extraction, and appraise the risk of bias; and reconcile their findings. We will pool data from similar studies using Mantel-Haenszel's fixed-issue model.
Ethics and dissemination This study is exempted from ethical consideration since the information collected are publicly available and at no point will confidential data from human participants be used. We will disseminate our results through publications in peer-reviewed journals and relevant conferences.
PROSPERO registration number CRD42018110505.
- Ebola vaccine
- Ebola virus illness
- haemorrhagic fever
This is an open admission article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work not-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, whatever changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/iv.0/.
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- Ebola vaccine
- Ebola virus disease
- haemorrhagic fever
Strengths and limitations of this study
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This review volition conduct an extensive search for inclusion of all types of study designs with no language restrictions thereby reducing option bias.
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A careful selection of studies, quality assessment and data extraction will be done in duplicate to ensure rigorous conduct of the review.
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This review will assess risk of bias from the different types of study designs using relevant Cochrane risk of bias tools.
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Meta-analyses of included studies may not exist appropriate to perform due to expected heterogeneity of the studies.
Background
Description of the condition
Ebola virus disease was first observed in the early on 1976 and since and so there have been a number of pocket-sized and large outbreaks.one Ebola virus belongs to a family of viruses known as Filoviridae, genus Ebolavirus where there are currently five species identified under this genus, namely Bundibugyo ebolavirus, Reston ebolavirus, Sudan ebolavirus, Tai forest ebolavirus and Zaire ebolavirus. two B. ebolavirus, R. ebolavirus, S. ebolavirus and Tai Forest ebolavirus are known to cause severe and often deadly haemorrhagic fever.2 The case fatality charge per unit of Ebola virus disease varies by species and could be as high as 90%.3 Ebola virus is normally found in animals known equally the fruit bat and transmission occurs through human contact with the tissue of fruit bats; ingestion of fruit bat faecal matter in contaminated h2o, food and plants and human-to-human transmission through actual fluids.4 Once a human host is infected with Ebola virus, the infection to disease mechanism starts with the virus implanting itself inside the body where it begins to replicate and spread to target organs where it continues to multiply leading to disease.five Ebola virus inside the body is enveloped in a lipid membrane that allows the Ebola virus to enter and spread inside the macrophages, monocytes and dendritic cells. When the virus reaches the liver and spleen, it damages the tissues either by directly cytotoxic effect or stimulating the immune system to overproduce toxic agents.four 5 Ebola virus has an incubation period of up to 21 days. Symptoms range from transient flu-similar episodes to septic shock and death.6
Description of the intervention
In June 2018, it was reported that in that location were nigh 36 completed Ebola vaccine trials and 14 ongoing trials at various stages of recruitment.7 Currently there are no Ebola vaccines that take received regulatory approval for use; however, the adulterate recombinant vesicular stomatitis virus vector vaccine (rVSVΔG-ZEBOV-GP) which has recently completed phase clinical trials has been granted admission to the Priority Medicine Scheme by the European Medicine Bureau and Breakthrough Therapy designation past the US Food and Drug Assistants.8 While ii other candidate vaccines, recombinant vesicular stomatitis virus-based (rVSV) plus human adenovirus type 5 vaccine (Ad5) prime heave (GamEvac-Combi) and recombinant adenovirus blazon v vector-based Ebola vaccine (Ad5-EBOV), take been licensed for emergency apply in Russia and People's republic of china, respectively.8 In addition, there are various candidate vaccines undergoing phases i–3 clinical testing.9
How the intervention might piece of work
Many of the Ebola virus candidate vaccines use recombinant vectors based on man adenovirus serotype and chimpanzee adenovirus serotype expressing envelope glycoprotein (GP) of Zaire Ebola virus.viii 10 11 Ad5-EBOV and Ad5 candidate vaccines are both non-replicative, recombinant human adenovirus serotype 5 expressing envelope GP of Zaire Ebola virus, withal Ad5 as well expresses envelope GP of Sudan Ebola virus as well.8 10 11 Adenovirus type-26 vector-based vaccine (Ad26.ZEBOV) is an adenovirus type-26 vector-based vaccine expressing envelope GP of Zaire Ebola virus species which is combined with modified vaccinia virus Ankara-Bavarian nordic (MVA-BN) Filo-vector vaccine (prime number/booster), where MVA-BN-Filo expresses four filoviruses nucleoproteins GP of Zaire Ebola virus, Sudan Ebola virus, Tai woods Ebola virus and the Marburg viruses, while recombinant chimpanzee adenovirus type 3–vectored vaccine (ChAd3-EBOZ) is a recombinant chimpanzee adenovirus type three–vectored vaccine expressing envelope GP of Zaire (Mayinga strain) Ebola virus species also combined MVA-BN filo-vector vaccine (prime/booster).8 10 xi Recombinant chimpanzee adenovirus type 3 vaccine (ChAd3) is a non-replicative recombinant chimpanzee adenovirus serotype 3 envelope GP of both Sudan Ebola virus and Zaire Ebola virus.8 11 12 DNA plasmid vaccines take several candidate vaccines that are either encoded for both the Zaire Ebola virus and Sudan Ebola virus or Marburg viruses.10 12 rVSVΔG-ZEBOV-GP and Recombinant Vesicular Stomatitis Virus-based Vaccine (VSV N4CT1 EBOVGP1) are both replicative and recombinant vascular stomatitis virus vaccines enveloping GP of Zaire Ebola virus, while GamEvac-Combi (rVSV & Ad5, prime/boost) is a replicative recombinant vascular stomatitis virus and human adenovirus serotype 5 vaccine expressing envelope for Zaire Ebola virus.eight 11 Nanoparticle recombinant Ebola GP vaccine is a nanoparticle recombinant vaccine with or without a matrix-adjuvant that is against the Zaire Ebola virus species, similar to this candidate vaccine is the DNA vaccine (INO-4212) which is delivered using an electroporation is as well confronting past and present Zaire Ebola virus strains.8 eleven Lastly, the HPIV3-EbovZ candidate vaccine is a live attenuated human parainfluenza virus type three vectored expressing GP of Zaire Ebola virus. Allowed responses from the utilise of these vaccine is observed in the follow-up catamenia of which the longest interval has been at least 12 months.eight
Why it is important to practise this review
In that location have been several trials investigating the effects of candidate Ebola vaccines including a systematic review of Ebola vaccine evolution which reviewed Ebola vaccine studies to assess factors associated with antibody response variability in humans,13 However there is no collective evidence of what the effects of the Ebola vaccines are. This review will provide a global view on inquiry conducted on Ebola virus vaccines. In addition, the review will investigate immune responses of participants mail vaccination and reasons for (in)efficacy of the vaccines also every bit unlike strategies employed in vaccinating participants.
Objectives
To appraise and summarise the effects of Ebola candidate vaccines including protection against the Ebola virus disease, the immune response and side furnishings in humans.
Methods
Inclusion criteria
We provide below the eligibility criteria for selecting studies, including the type of studies, participants, interventions and outcomes.
Types of studies
Randomised trials, not-randomised trials, instance-controlled studies and accomplice studies.
Types of participants
The report will include just man participants regardless of any identifying characteristics such equally historic period, gender, demographics and socio-economic status.
Types of interventions
Vaccination with whatever candidate vaccine, including only not limited to the following:
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Adulterate recombinant vesicular stomatitis virus (rVSV) vector vaccine.
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Recombinant adenovirus blazon 5 vector-based Ebola vaccine (monovalent).
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Recombinant vesicular stomatitis virus-based and man adenovirus type v vaccine.
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Recombinant adenovirus blazon v vector-based Ebola vaccine (bivalent).
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Adenovirus type-26 vector-based vaccine (Ad26.ZEBOV) with modified vaccinia virus Ankara-Bavarian nordic (MVA-BN) filo-vector vaccine.
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Recombinant chimpanzee adenovirus type 3 vaccine (monovalent).
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Recombinant chimpanzee adenovirus type 3 vaccine (bivalent).
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Recombinant chimpanzee adenovirus type 3–vectored vaccine (cAd3-EBO and cAd3-EBOZ) with modified vaccinia virus Ankara-Bavarian nordic (MVA-BN) filo-vector vaccine.
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Recombinant vesicular stomatitis virus-based vaccine.
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Glycoprotein nanoparticle vaccine (EBOV GP) with or without Matrix-Thou adjuvant.
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DNA vaccine (INO-4212).
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Live-attenuated human parainfluenza virus type vaccine.
The comparison interventions will be placebo, no intervention or some other vaccine.
Types of outcomes
Primary outcomes
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Incidence of Ebola virus affliction.
Secondary outcomes
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Immunogenicity (measured by virus neutralisation analysis).
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Adverse events post-obit vaccination (serious adverse events, minor adverse events).
Adverse events are effects of any severity where in that location is a possible causal relationship betwixt intervention and the event is identified equally reasonable.14 Adverse events can be solicited (predictable) or unsolicited (unexpected). Serious agin events are adverse effects severe enough to pb to harm, life threatening, requiring hospitalisation or prolonged infirmary stay, disability or incapacity, or decease of participant attributable to the intervention.fourteen
Search methods for identification of studies
We will search all potential studies (published, unpublished, in press and in progress) with no linguistic communication or date restrictions on the search strategy.
Electronic searches
The following databases and sources volition be searched to identify published main studies: Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; and Scopus. We will too search the WHO International Clinical Trial Registry Platform (WHO-ICTRP) for ongoing and completed trials using the search terms "Vaccines" OR "Vaccine" AND "Ebola". Should a trial from the registry be reported complete, the trial record will be checked for reported publications in the "URL to publication" field within the record or using the trial registration ID number to search electronic databases, and by contacting the investigators to ask if results are available for sharing. We provide the proposed search strategy for PubMed in table i.
View this table:
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Tabular array i
Proposed PubMed search strategy
Searching other resources
We will search the CDSR and DARE for related reviews, too as the reference lists of relevant reviews and other studies.
Data drove and analysis
Choice of studies
Two review authors will independently screen titles and abstracts of all identified studies in the combined search output for potentially eligible studies and exclude clearly irrelevant studies. Full texts will be retrieved for potentially eligible studies and 2 review authors will independently assess the full text for inclusion into the review using predefined inclusion criteria. The review authors will resolve whatever disagreements through a discussion, should they fail to resolve the differences, a third review writer will pass on judicially for consensus. The study choice process will be recorded in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) diagram and all potentially eligible studies excluded through full text screening and will be listed in a tabular array describing characteristics of excluded studies with reasons for exclusion.
Information extraction and management
A data extraction form will be designed and piloted by two review authors for validation. The ii review authors will extract data independently and in indistinguishable from each included study. Two reviewers will come across to compare and combine data extracted. Where there are disagreements, a discussion volition be held in guild to reach consensus, should an agreement not be reached, a third review author will pass on judicially. The following characteristics of the study will be extracted:
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Study setting, design, sample size, power calculation and trial registration.
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Baseline characteristics including weight, age, sex activity, HIV status and other comorbidity.
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Intervention vaccine and command vaccines dosages, routes of administration and times of vaccinations.
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Outcomes measures.
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Findings (incidence, immunogenicity, adverse events data).
Assessment of risk of bias in included studies
Two review authors will independently use the Cochrane Effective Practice and Organization of Care (EPOC) tool to assess risk of bias of included studies in duplicate. Disagreements volition exist resolved through give-and-take until consensus is reached. Where necessary a third review author will exist consulted to resolve whatever disagreements. The two review authors will pilot the run a risk of bias tool on four included studies to ensure consistency in assessing the studies. The EPOC tool has nine listed domains to appraise chance of bias for both randomised and not-randomised trials and these include the following: random sequence generation, allotment concealment, blinding of outcome assessors, incomplete effect data, knowledge of the allocated interventions adequately prevented during the study, selective reporting, baseline characteristics like, costless of contamination, baseline outcomes similar and other biases, all the domains are fully described in EPOC 2017.15 The review authors will consider a study as having a depression take a chance of bias if all criteria defined by EPOC are scored as 'yes', an unclear adventure of bias volition be a study in which one or more criteria are scored every bit 'unclear', Lastly, a high hazard of bias will be a written report in which one or more criteria are scored as 'no'. For not-randomised studies of interventions (Cohort and case controlled studies) we volition use the ROBINS-I tool to assess the risk of bias which includes iii additional domains to those of the EPOC tool namely, confounding, selection of participants into the report and classification of the intervention16 .
In add-on, nosotros will use a funnel plot to assess publication bias.
Measures of handling issue
Nosotros volition analyse all data from included studies using RevMan V.5.3.17 Nosotros will combine dichotomous data using risk ratio (RR) or ORs with their 95% Cls and volition limited continuous outcomes as standardised mean differences with their 95% Cls. Nosotros will attempt to group studies reporting geometric means and ab titres to analyse separately
Unit of analysis issues
For included studies that have multiple interventions we volition utilize the Cochrane-handbook department 16.5.iv every bit a guideline to avert unit of measurement-of analysis fault and section 16.6.iii for multiple-handling meta-analysis.xviii Nosotros will analyse the information by combining treatment arms or past splitting the control group so that participants are only included in one case in the meta-assay.
Dealing with missing data
If at that place is missing data in the included studies, we will assess whether the missing information is related to outcomes and contact the trial authors for more data. We will perform intention to treat analysis to business relationship for missing data of important outcomes.
Assessment of heterogeneity
Nosotros will appraise the data extracted to find key differences in the setting, population groups, intervention blazon, dosages, route of administration, and timing of vaccination. We will also consider degree of risk of bias in the studies, upshot measurement procedure, and assess variation in treatment effects.xviii We will inspect the woods plot for overlapping Cls and the following data to determine the level of heterogeneity: χ2p-value significance of ≤0.ane and an I2 statistical value of more than 50% every bit likely heterogeneity.
Data synthesis
We will stratify analyses by study design and pool information from studies with identical designs, candidate vaccines and outcomes using the fixed-upshot Mantel-Haenszel model for meta-analysis. For the meta-analysis of agin event outcomes, we volition option a maximum of 3 of the near frequent adverse events that were considered to be serious. Should a meta-analysis not be applicative due to heterogeneity of the studies, we will requite a narrative report instead. Nosotros will also endeavor to perform statistical adjustments for sample size and variance for whatever cluster randomised trials before meta-analysis if appropriate.
Subgroup analysis and investigation of heterogeneity
We will explore heterogeneity in the studies and perform subgroup analysis by:
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Age of participants that is, children versus adults.
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Pregnancy status that is, pregnant versus not meaning.
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Comorbidities such equally HIV status status that is, pregnant versus not pregnant.
Random-upshot analysis will be considered in the meta-analyses if meaning statistical heterogeneity in subgroup analyses cannot be explained. Nosotros will define significant statistical heterogeneity at the χ2p value of ≤0.1 and an I2 value of more than than l%.
Sensitivity analysis
If studies have incomplete effect data that renders the study to have high risk of bias, we may use imputation and perform sensitivity analysis to appraise the impact of the missing data. We will likewise consider risk of bias assessment and weighing of the studies included in the meta-analyses to perform a sensitivity assay.
Certainty of evidence
We volition use Grading of Recommendations Assessment, Development, and Evaluations (GRADE) to assess the certainty of prove. Using the GRADEpro tool nosotros volition construct a 'summary of findings' table for each outcome of the pooled studies.19
Timelines for the review
This protocol was written following the recommendations by the relevant PRISMA guidelines.twenty Nosotros registered this study in the International Prospective Register of Systematic Reviews in Oct 2018.21 We planned to develop the search strategies, conduct preliminary searches, and pilot study selection processes between Feb and May 2019. Nosotros plan to finalise study selection, extract data from included studies, and conduct data analyses between June and December 2019; and prepare and submit the manuscript to a peer-reviewed journal by Jan 2020.
Patient and public involvement
At that place was no patient or public involvement in the grooming of this protocol.
References
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Source: https://bmjopen.bmj.com/content/9/7/e029617
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