- Formal science & Physical science
- EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain.
EBOLA VACCINE. VSV-EBOV rapidly protects macaques against infection with the 2014/15 Ebola virus outbreak strain. Essay Example
- Category:Formal science & Physical science
- Document type:Assignment
A Critical Review of Ebola Vaccine. VSV-EBOV Rapidly Protects Macaques against Infection with the 2014/2015 Ebola Virus Outbreak Strain
Summary of Background and Contents
The 2013 Ebola Virus (EBOV) outbreak in Western Africa started in Guinea and then spread to neighboring countries mainly Liberia and Sierra Leone. The outbreak caused a global health care crisis since there was a high infection rate among the public and healthcare workers with official statistics indicating around 27,200 cases reported and over 11,100 deaths (World Health Organization). This outbreak was characterized by challenges in evacuating infected or exposed health workers, logistical issues, lack of sufficient medical supplies, and financial constraints. Following the outbreak, current experimental efforts were advanced to clinical trials such as the VSV-EBOV vaccine, which had been shown to have significant efficacy and satisfactory safety profile during pre-and-post exposure vaccination in macaque and rodent models (Regules et al.). Phase 1clinical trials for VSV-EBOV in humans were conducted in different parts of the world, indicating that it was safe and immunogenic and therefore there was a need for efficacy tests.
For the EBOV Makona strain outbreak in West Africa, there was still no preclinical efficacy data for any EBOV vaccines that were under phase 1 clinical trials. Furthermore, an analysis of the sequence data for EBOV strain in Sierra Leon during the West African outbreak indicated that the EBOV was undergoing a higher mutation rate (Gire et al., 1370). As a result, the current vaccines that were under experimentation could not be guaranteed to be applicable for the EBOV-Makona strain. This research, therefore, sought to determine whether the current vaccines were applicable for the EBOV-Makona strain in West Africa by conducting efficacy testing through a cynomolgus macaque challenge model in which the researchers used good manufacturing practice (GMP)-grade VSV-EBOV.
Fifteen cynomolgus macaques were allocated to groups of two or three in a random manner and then vaccinated with a single intramuscular injection for GMP grade VSV-EBOV on a different day prior to the challenge (28, 21, 14, 7, and 3 days). The control group for the study consisted of 3 animals which were vaccinated with VSV-Marburg virus vaccine (VSV-MARV) 28 days before the challenge (VSV-MARV does not protect against EBOV challenge). The animals were continuously monitored on a daily basis and blood was sampled and clinically examined on a weekly basis indicating normal behavior and lack of any side effects after vaccination. The challenge was administered as a lethal dose of EBOV-Makona through intramuscular injection to the opposite leg. The animals were intensely monitored and examined during the 42 days of the challenge or up to when euthanasia was necessary due to the progression of the disease. For euthanasia cases, the study relied on standards stipulated by the Institutional Animal Care and Use Committee to assess when the animals had to be humanely euthanized.
After the start of the challenge, the animals from the control group vaccinated with VSV-MARV and one animal from the three-day GMP grade VSV-EBOV vaccinated group developed classical severe EHF characterized by thrombocytopenia, macular cutaneous rash, a rise in levels of liver enzymes and viremia. These animals were euthanized after 5,7,7, and 8 days into the challenge. One animal from the 3-day vaccinated group showed moderate symptoms of EHF (mild rash and viremia) but did not progress to a point where humane euthanasia was necessary and managed the virus by day nine with eventual survival. The other animal from the 3-day vaccinated group showed very mild symptoms of disease with no rash or viremia and had a quick recovery. For the other nine animals in the -28, -21,-14, and -7 day vaccinated groups had no clinical symptoms of disease, did not show EBOV viremia, and had no unusual changes in liver enzymes or hematology, and were totally protected from the lethal EBOV-Makona challenge.
The study findings indicated that vaccination with VSV stimulated the activation of macrophages and NK cells. NK cells have been associated with survival against EBOV infections (Fieldmann et al. 858). Despite the fact that EBOV-VP35 and EBOV-VP24 proteins pose potent IFN antagonistic activity, the stimulation of innate immunity following the VSV vaccination might contribute to the creation of an antiviral environment in the host which inhibits EBOV replication during the challenge. Since VSV-MARV-vaccinated group also indicated increased levels of IFN-g at day three of the challenge which was probably initiated by EBOV-Makona infection and did not have immunity, this shows that innate immune responses might not be able to cause immunity against lethal EBOV infection alone. In comparison, the 3-day vaccinated animals had significant EBOV-GP-specific IgG and IgM antibodies at day 6 and day 3 into the challenge, respectively, contributing to immunity. As such, VSV-EBOV activation of innate immune responses may inhibit virus replication during the critical moment necessary for the development of the relevant adaptive responses and especially antibodies.
Using a gold standard macaque disease model for Ebola hemorrhagic fever (EHF), the study successfully established the GMP-grade VSV-EBOV’s preclinical efficacy data that can help establish the necessary measures for the West African EHF. When macaques were administered with a single high dose vaccine of GMP-grade VSV-EBOV under the same procedures used in phase 1 clinical trials and also used in administering vaccine trials in West Africa (Merzi et al), there were no adverse effects in the macaques. This supports the minor adverse effects that were accounted for in phase 1 clinical study in human volunteers in centers across America, Europe, and Africa when they were administered, with the VSV-EBOV vaccine (Agnandj et al; Regules et al; Lai et al. 1253). VSV-EBOV has a very short time to immunity and it only offers a limited immunity against lethal diseases despite cases whereby it was administered 3 days prior to the challenge. VSV-EBOV vaccination seemed to initiate a strong natural immune response that could be in the form of macrophage activation and NK cell-mediated inhibition of EBOV replication prior to the development of specific adaptive reactions. Based on these results, there is a need for further human-based clinical trials using GMP-grade VSV-EBOV focusing on safety and immunogenicity as well as the continuation of the clinical trials in West Africa.
The outline clearly outlines the aims of the study with a clear and concise explanation of the techniques used, results, and the conclusion of the study. It outlines how the study seeks to determine whether the VSV-EBOV vaccine ,which had been shown to have clinical efficacy could be applied against the West African EBOV-Makona strain (Merzi et al., 739). It also describes the methods used, including the dosages administered, the results obtained and the conclusions that were arrived at based on the results obtained.
In the introduction, there is sufficient coverage of the background culminating in the need for this particular study. The introduction captures the outbreak of the Ebola virus in West Africa and how the virus spread from Guinea to other neighboring countries, mainly Sierra Leon and Liberia (World Health Organization). It concisely presents the actual scale of the outbreak, including the lack of adequate medical supplies, the high infection rate and death rates, worldwide response to new cases and particularly the evacuation of infected or exposed aid workers. The results from Sierra Leon indicated that the EBOV virus was rapidly mutating during the West African outbreak compared to previous rates of mutation, although later results from Mali indicated the mutation rate of EBOV in the region to be similar to previous rates recorded in other outbreaks (Gire et al., 1370; Hoenen et al. 118). The research question of this particular study was based on whether the experimental interventions such as VSV-EBOV were applicable in addressing the West African EBOV-Makona strain. The introduction also captures the topic area by establishing the West African EBOV-Makona outbreak and the continued search for vaccinations against the Ebola virus.
Materials and Methods
This study sought to establish whether the VSV-EBOV vaccines that were currently under development could be applied in countering the EBOV-Makona outbreak in West Africa. As such, the study used methods that had been used in other recent phase 1 clinical trial such as the highest lethal immunization dose (Merzi et al.). The research clearly provides a detailed account of all methods used in the study with all key pieces of information relevant to the study being mentioned (Agnandj et al.). For the methods that were developed by other researchers in previous studies, there are references acknowledging those works. For the new methods developed by the authors of this study, there is a detailed account of the procedures and measures taken to help accomplish the study. The experiments in this study are very good as they included a control group. The methods used in the experiments are also clearly explained.
The results of the study are clear and detailed enough to show the outcomes of the study. The results are also presented in a logical order such that they are easier to understand and interpret. All the results from the study are clearly represented in figures. The results of the study are fairly sound given that the sample size used for this study was too small. With a total study sample consisting of only 15 animals, sample groups were made of either 2 or 3 animals and this may not be a very representative sample. The figure legends clearly describe the figures and the statistics used in the study.
The interpretation of the results is very good as the study provides a step by step explanation of how the conclusions in the study were arrived at. The authors have clearly drawn the line between their own results and results obtained by others when presenting their discussion (Fieldmann et al.). The authors were comprehensive when discussing their findings ensuring that all relevant results, whether positive or negative were featured without omission. The authors clearly and comprehensively discussed their findings and conclusions based on the study findings and the available literature on the topic (Agnandj et al.; Fieldmann et al.; Regules et al.; Lai et al. 1253). The study findings are in agreement with these other studies in the field. The authors provided a very sound conclusion which is supported with detailed explanations and evidence that guided them to arrive at these particular conclusions. As such, their conclusions are acceptable and clearly represent the actual case.
All statements featured in the paper that are owned by different authors were appropriately referenced. The author has referenced a broad base of studies conducted by other researchers without preference to only the works of the author. The study referenced all the relevant studies on this topic which had been carried out prior to this study (Dhaked, Ram Kumar; Agnandj et al.; Fieldmann et al.; Regules et al.; Lai et al, 1253).
Tables and Figures
All Figures in the paper were supported with detailed and clear legends such that they are easily understood without having to keep referencing back to the text. However, to the average reader, the figures use complex statistical interpretations.
Ethics and Conflicts Of Interest
Since the study used animals as test subjects, the study was approved by the Institutional Animal Care and Use Committee. The study declares all parties with interest in the study, including financiers, regulatory bodies, the vaccine manufacturer, and declares that there are no competing financial interests among the authors.
Agnandji, Selidji T., et al. «Phase 1 trials of rVSV Ebola vaccine in Africa and Europe.» New England Journal of Medicine 374.17 (2016): 1647-1660.
Dhaked, Ram Kumar. «Re-Emergence of Zaire Ebola Virus Disease: Lessons to Be Learnt». Journal of Bioterrorism & Biodefense, vol 06, no. 02, 2015, OMICS Publishing Group, doi:10.4172/2157-2526.1000e116.
Feldmann, H., et al. «Effective Post-Exposure Treatment of Ebola Infection.» PLOS Pathog. 3, e2 (2007)
Gire, Stephen K., et al. «Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak.» science 345.6202 (2014): 1369-1372.
Hoenen, T., et al. «Mutation rate and genotype variation of Ebola virus from Mali case sequences.» Science 348.6230 (2015): 117-119.
Lai, Lilin, et al. «Emergency postexposure vaccination with vesicular stomatitis virus–vectored Ebola vaccine after needlestick.» Jama 313.12 (2015): 1249-1255.
Marzi, A. et al. «VSV-EBOV Rapidly Protects Macaques against Infection with the 2014/15 Ebola Virus Outbreak Strain». Science, vol 349, no. 6249, 2015, pp. 739-742. American Association for the Advancement of Science (AAAS), doi:10.1126/science.aab3920.
Regules, A. et al. «A Recombinant Vesicular Stomatitis Virus Ebola Vaccine — Preliminary Report» New England Journal of Medicine. 10.1056/NEJMoa1414216 (2015).
World Health Organization (WHO), “Ebola situation report, 3 June 2015,” http://apps.who.int/ebola/ebola-situation-reports (2015)
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