MMS2102: Literature Review on Ebola Virus, Vaccines, and Global Health

This literature review examines the Ebola virus, a significant global health concern, focusing on its characteristics, pathogenicity, and the progress of vaccine development. It delves into the Ebola virus, discussing its outbreaks, symptoms, and modes of transmission. The review explores the different vaccine formats, with a particular emphasis on the rVSV-ZEBOV vaccine, discussing its efficacy, side effects, and the ring vaccination strategy. It also analyzes the challenges in developing effective vaccines, including the virus's rapid mutation rate. The review highlights the efficacy rates of various vaccines and the potential for future advancements, including genetic engineering to improve vaccine longevity and booster vaccinations, which are crucial for achieving optimal immune responses and controlling the spread of the disease. The document provides valuable insights into the current state of Ebola research and the ongoing efforts to combat the disease.

Ebola

Table of Contents
Introduction.................................................................................................................................................3
What is Ebola virus?...................................................................................................................................3
Ebola pathogencity:.....................................................................................................................................4
What is vaccine............................................................................................................................................4
Ebola vaccine format...................................................................................................................................5
Side effects of Ebola vaccine.......................................................................................................................6
Efficacy of Ebola vaccines............................................................................................................................7
Possible advancement of Ebola vaccine......................................................................................................8
Conclusion...................................................................................................................................................8
References.................................................................................................................................................10

Introduction
The ebola disease is becoming a serious threat in recent years caused by Ebola group of viruses.
Based on the various reports of outbreaks Ebola was found reportedly in the United States,
Ivory Coast, Sudan, Democratic Republic of the Congo and surprisingly some places of Europe
Continent. The symptoms of Ebola disease are observed within 2 to 21 days depend on the body
immunity system. There are no such preventive vaccines are officially announced by the world
health organization, but some preventive care processes are prescribed by the doctors for the
community where chances of spread are high. The present study will emphasize on few
literatures to write a review on Ebola virus and its effects. The study will discuss the progress in
vaccination formulation process and side effects of them in human body along with the future
possibilities to reduce the Ebola endemic condition.
What is Ebola virus?
The disease caused by Ebola viruses can be considered as the rare and fatal one for the human
and non human primates. Sudan, Ebola, Bundibugyo, Tai Forest are the four disease causing
viruses in the genus of Ebola and they are responsible for causing Ebola disease within humans.
Fruit bats are natural hosts of Ebola viruses and the direct or indirect contact of saliva, body fluid
secretion; feces of bats may cause Ebola disease to humans and nonhuman primates. Broken
skin, mucous membranes of infected human is the cause of direct
transmission of disease from human to human. It is a single stranded
RNA virus as it carries negative sense RNA genome within
cylindrical virions ("What is Ebola Virus Disease? | Ebola (Ebola
Virus Disease) | CDC", 2019). Ebola virus contain viral envelope
which is made by protective glycoprotein components. One of the
special natures of this group of viruses is that they can mutate their
genomes rapidly and this is the reason why no such vaccines are
developed till date. The cholesterol-transporter protein (NPC1) in primates is the place of entry

of the virus through which it release its RNA genome into host cells and starts replication,
transcription and translation to produce GP1 and GP2 proteins which is essential for
nucleocapsid formation. At the end, the nucleocapsid and viral envelope react with host cell
membrane and destroy blood cells rapidly (Nichols, 2019).
Fig: 1, structure of Ebola virus
Source: (Gavish, 2019)
Ebola pathogencity:
The outbreak of Ebola virus disease was first observed in Democratic Republic of the Congo in
the year 1976. After that the outbreaks was observed in various places in Africa. Some other
modes of transmission of this contagious disease are blood, feces, vomit of infected persons. In
the year 2014, the outbreak of Ebola disease was the largest one with approximately 11000
deaths of humans in South Africa. The main affected area was Northern Liberia, Guinea, and
Sierra Leone. In 2018, the Ebola outbreaks were observed in Democratic Republic of the Congo
with more complexity. Common symptoms in humans are diarrhea, vomiting, fever, headache,
joint aches, red eyes, no appetite, stomach pain, difficulty in breathing and swallowing etc.
elevated amount of liver enzyme, lower amount of white blood cells, and lower amount of
platelets will be seen from the pathology examination of infected persons. ELISA, PCR,
Isolation of Virus is the laboratory based diagnosed procedures. At the initial stage of the disease
patients should bring to the hospitals to check the balance of body fluids, oxygen level and
pressure. Infected person need to be separated from others to prevent the contamination of the
Ebola disease. It is important to sterilize the needles and other health care objectives before
disposing them("Ebola virus disease", 2019).
What is vaccine
It is important to understand how vaccines work to fight with viruses before emphasizing on
experimental ebola vaccines. A vaccine helps the body's immune system to recognize the

harmful pathogens like viruses or bacteria by inserting certain molecules from the pathogens
into blood cells. The molecules are called antigens. As a result the host body’s immune system
stimulate B and T cells and produce antibodies against pathogens and most importantly immune
system produce lots of memory cells for future. When respective virus or bacteria attack human
body, memory cells come forward and activate the immune system to destroy the pathogens in
an immediate basis. Most important thing to be noticed that vaccine is not only work on
individual human beings but protects the entire community. It is called Herd immunity and ring
vaccination, a major form of vaccination in the Ebola cases is related to the hard immunity
process. Live attenuated vaccines are the most effective form of vaccines which help immune
system to produce lifelong memory cells against the virus.
Ebola vaccine format
Lots of vaccines against Ebola viruses have been experimented already but none of them are not
100% successful in terms of curing the disease. The main reason behind this is that the genome
of the virion is being mutated frequently. The other reason is the strong envelope outside the
virion that protect the RNA genome. However, based on the literature reviews, among all of the
experimental vaccines, rVSV-ZEBOV ebola vaccines is supposed to be a most successful
one("How Vaccines Work | PublicHealth.org", 2019). It is a kind of recombinant and replication
competent vaccine by obtaining the genetically engineered vesicular stomatitis virus genome to
obtain the ebola virus glycoprotein. This vaccine uses live attenuated form of vesicular stomatitis
viral cell where gene of envelope glycoprotein is replaced by the Ebola envelope glycoprotein
gene. Based on the result data provided by WHO and INRB institute of Democratic Republic of
the Congo, in the 2018 outbreaks the rVSV-ZEBOV Ebola vaccine was successfully
administered to the community through ring vaccination format and the success rate was 97%
("Ebola vaccine provides protection and hope for high-risk communities in the Democratic
Republic of the Congo", 2018).

Fig: 2, recombinant vaccine formation in general
Source: ("Ebola vaccine", 2019)
Side effects of Ebola vaccine
As live attenuated vaccines are derived from part of disease causing pathogen thus there is a
chance of showing some mild to medium amount of adverse effects in the human body. This is
because our immune system needs time to accustom with foreign antigens and create memory
cells. Some common adverse reactions that are associated with this type of vaccines are allergy,
mild fever, muscle pain, sensitivity to some food products like eggs, prawns etc. High amount of
cytokines secretion from T-helper cells of the immune system are the reason behind these
inflammatory responses.
Based on the literature reports, most of the Ebola vaccines have shown adverse effects in the
human body. The side effects are observed in candidates by observing them for 30 minutes
after vaccination and after three days. The side effect of latest rVSV-ZEBOV ebola vaccine is
mild to medium with muscle pain, headache, fatigue, mild fever. These symptoms can be treated
with acetaminophen medicine (Agnandji et al.,
2016). There were two evidences of serious illness
noted during vaccination. One is anaphylaxis which
is one kind of allergy response and another one is
diseases caused by influenza. Though there was no
data of mortality due to these side effects. But the

scenario was not the same for every experimental vaccine. Some of them were showing even
death when they were experimenting on mice. For instance, Ebola GP vaccine was trialed in the
year of 2014 where glycoprotein nanoparticle was engineered in mice recombinant DNA. The
result was showing 100% success rate on rhesus monkey but it is highly antigenic to the human
body. Though the rVSV-ZEBOV Ebola vaccine protects human in an extent level but there are
certain amount of scientific researches still need to continue to achieve the license from the
government (Ledgerwood et al., 2017).
Fig: 3, schematic diagram of rVSV-ZEBOV vaccine formation
Source: (Medaglini & Siegrist, 2017)
Efficacy of Ebola vaccines
Practically there is no such licensed vaccine has been appeared till date in the market. All of
them are in the level of trial research procedures. Most of them have shown lethal effects when
injected into the white blood cells in the laboratory. VSV-EBOV has shown 70% efficacy
against the virus in December 2016 after several trials. Also, the research design of the
vaccination study in this case was in a question mark. CAd3-EBO Z vaccine was trialed in three
phases and the third phase has shown significant efficacy rate in the year 2015 without any safety
issues. But there were several other issues arise and the experimental vaccines have shown
unstable antibody production in the human immune system. Though the efficacy rate in
chimpanzee was almost 100% (Metzger & Vivas-Martínez, 2018).
Among all of the experimental Ebola vaccines, rVSV-ZEBOV has the highest efficacy rate with
minimal side effects. Most of the other vaccines have shown protection of the non human
primates like chimpanzees, monkeys etc. but these vaccines are inefficient to the human body.
From august 2018 to March 2019 experimental ring vaccination procedures were organized in
Democratic Republic of the Congo through 679 rings facilitation. According to the data, rate of

Ebola attack was 0.017% for vaccinated individuals. Whereas, chances of Ebola attack for the
unvaccinated individuals was 0.656%. The overall efficacy of ring vaccination of rVSV-
ZEBOV in the year of 2018 to 2019 was found 97.5% approx. it should be noted that, there
were 9 deaths among 56 Ebola attacked cases were reported within 9 days of ring
vaccination. From the above statistical data it can be concluded that ring vaccination of rVSV-
ZEBOV has shown the highest efficacy rate against Ebola disease. The strategy of ring
vaccination was successful because of the high coverage and rapid given protection in the rings.
There were no deaths reported after more than 10 days of vaccination (Wong, 2019).
Possible advancement of Ebola vaccine
After phase three trials of Ebola vaccine named rVSV-ZEBOV that have been shown the highest
rate of efficacy, submitted detailed documentation to the WHO secretariat for approval. Though
the rate of efficacy has still not achieved 100% and there must be some kinds of research work
needs to be done in order to achieve the best result in the recombinant DNA technology
method. Before crossing the hurdle of the licensing procedure, the secretariat of WHO have
implemented a research plan with the procedures to prevent epidemics ("Ebola Vaccines | NIH:
National Institute of Allergy and Infectious Diseases", 2019). This plan includes deliberations
by the genetic engineering experts and few more clinical trials of Ebola vaccines. WHO
mentioned to take notes of each individual about the post vaccination symptoms for ten days or
more? It is important to notice the duration of immune responses and the production of memory
cells. Based on the previous trials the duration was noticed about one year after vaccination after
single dose administration to the individuals. Thus, researchers need to concentrate to create the
genetic engineering process in order to increase the duration of the self immune responses. Also,
researchers should determine the total amount of dosage of the vaccine to obtain the maximum
memory cells production in the immune system of the body. Booster vaccination process must be
implemented in the vaccination procedure to achieve the highest success rate (Graham, 2019).

Conclusion
Ebola disease has been found to be an issue of concern in recent years for the medical and
research world. Because of the rapid mutation tendency of the Ebola group of viruses it has
been found to a most difficult process to obtain the effective vaccine format. After several trials
of different vaccines, rVSV-ZEBOV can be considered as the most efficient one with 97.5%
efficacy rate. The ring vaccination with live attenuated recombinant vector of Ebola has been
found to be the most desirable format to obtain the Herd immunity in the disease effective areas.
From this literature review it can be concluded that rVSV-ZEBOV ebola vaccine can be
considered as the most efficient vaccine against Ebola disease in the near future. Though there
are lots of research work must be done by the researchers in order to achieve the 100%
efficacy rate.

References
Agnandji, S., Huttner, A., Zinser, M., Njuguna, P., Dahlke, C., & Fernandes, J. et al. (2016).
Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe. New England Journal Of
Medicine, 374(17), 1647-1660. doi: 10.1056/nejmoa1502924
Ebola vaccine provides protection and hope for high-risk communities in the Democratic
Republic of the Congo. (2018). Retrieved 29 August 2019, from https://www.who.int/news-
room/feature-stories/detail/ebola-vaccine-provides-protection-and-hope-for-high-risk-
communities-in-the-democratic-republic-of-the-congo
Ebola vaccine. (2019). Retrieved 28 August 2019, from
https://en.wikipedia.org/wiki/Ebola_vaccine#/media/File:Recombinant_formation_of_plasm
ids.svg
Ebola Vaccines | NIH: National Institute of Allergy and Infectious Diseases. (2019). Retrieved
29 August 2019, from https://www.niaid.nih.gov/diseases-conditions/ebola-vaccines
Ebola virus disease. (2019). Retrieved 29 August 2019, from
https://www.who.int/news-room/fact-sheets/detail/ebola-virus-disease
Gavish, S. (2019). Ebola Virus - Symptoms, Pictures, Structure, facts and History. Retrieved 28
August 2019, from https://www.primehealthchannel.com/ebola-virus-symptoms-pictures-
structure-facts-and-history.html
Graham, J. (2019). Ebola vaccine innovation: a case study of pseudoscapes in global
health. Critical Public Health, 29(4), 401-412. doi: 10.1080/09581596.2019.1597966
How Vaccines Work | PublicHealth.org. (2019). Retrieved 29 August 2019, from
https://www.publichealth.org/public-awareness/understanding-vaccines/vaccines-work/
Ledgerwood, J., DeZure, A., Stanley, D., Coates, E., Novik, L., & Enama, M. et al. (2017).
Chimpanzee Adenovirus Vector Ebola Vaccine. New England Journal Of
Medicine, 376(10), 928-938. doi: 10.1056/nejmoa1410863
Medaglini, D., & Siegrist, C. (2017). Immunomonitoring of human responses to the rVSV-
ZEBOV Ebola vaccine. Current Opinion In Virology, 23, 88-94. doi:
10.1016/j.coviro.2017.03.008
Metzger, W., & Vivas-Martínez, S. (2018). Questionable efficacy of the rVSV-ZEBOV Ebola
vaccine. The Lancet, 391(10125), 1021. doi: 10.1016/s0140-6736(18)30560-9
Nichols, H. (2019). Ebola: Symptoms, treatment, and causes. Retrieved 29 August 2019, from
https://www.medicalnewstoday.com/articles/280598.php
What is Ebola Virus Disease? | Ebola (Ebola Virus Disease) | CDC. (2019). Retrieved 29 August
2019, from https://www.cdc.gov/vhf/ebola/about.html

Wong, G. (2019). Progress in Elucidating Potential Markers and Mechanisms of Rapid
Protection Conferred by the VSV-Vectored Ebola Virus Vaccine. Mbio, 10(4). doi:
10.1128/mbio.01597-19