Javaney Thomas
ENGL 21003
Professor Michael Grove
5/24/18
Final Research Paper

How the Study of Epidemiological Factors and Genetic Diversity aids in the Development of An Ebola Vaccine
Viruses evolve over periods of time, by mutation, recombination and reassortment . One such virus that has evolved continuously and caused a pandemic, is the Ebola virus of the filovirus family. Genetic drift makes it difficult for the Ebola virus to be vaccinated because it evolves rapidly, however this evolution is not a functional change of the virus but simply a genetic one. Scientists should abandon all efforts of creating the vaccine based on the functional changes of Ebola and instead, focus their efforts on better understanding the epidemiological factors and genetic changes of the virus to increase our chances of creating an Ebola vaccine.
The Ebola virus gained significant prevalence in Guinea of March 2014 which later affected Sierra Leone and Liberia with “thirty-six confirmed cases…from Italy, Mali, Nigeria, Senegal, Spain, the United Kingdom, and the United States.” “In this period, there were 28,616 human cases, of which 11,310 people died.” Prior to this outbreak, there had already been a documented case of the Ebola virus in northern Zaire now known as the Democratic Republic of the Congo. This happened “between the 1st of September and the 24th of October 1976”, where “318 cases of acute viral hemorrhagic fever”, resulted in “280 deaths, and only 38 serologically confirmed survivors.” Now, one must wonder why the Ebola virus has a high mortality rate when we have been familiar with it for over 40 years. While it is true that scientists have yet to develop an effective vaccine for the Ebola virus, this is not due to incompetence, but rather to the persistent evolution of the virus. The virus has continued to genetically modify causing genetic diversity within infected persons and between individuals (in transmission). This means the virus is evolving within human hosts to the point of genetic drift, which is when a virus is far removed from its original ancestor in molecular and genomic structure. According to Aboyami S. Olabode et al., “functional adaptation,”- (not functional change)- “of the virus in the human host has already occurred” and “the Ebolavirus is evolving but not changing.” In other words, the ebolavirus is very efficient in its virulence as genetic drift allows it to develop through transmission, recombination etc., but the effects it has are the same. As said before, one of the many reasons why the vaccine is so difficult to synthesize is because the virus has “functionally adapted” to humans. This was concluded due to the exhaustive amount of genetic variation found among infected patients, which was exclusive to the 2014-15 outbreak, and the spike in fatalities and infections compared to the initial 1976 outbreak. This rise in virulence could be interpreted as the virus evolving, and while it has, it only has done so on a molecular level, there has been no new symptoms or ways of transmission to support a “functional change” in Ebola. Olabode’s research computationally analyzed the amino acids responsible for the creation of the new Ebola virus disease (EVD) genomes and found “35 that have non-synonymous nucleotide changes” which means 35 different proteins. Of these, the important proteins are (GP), Viral Matrix Protein (VP40) and VP30.
Detailed by Daniel J. Park et al., “Ebola Virus Disease (EVD) is caused by the Makona variant of the Ebola virus (EBOV).” (EVD), has two distinct lineages in the Makona genome, a part of the Ebola gene sequence. These lineages known as SL1 and SL2, have developed 232 new different Makona genomes since the beginning of the outbreak in late 2013. “SL2 had four mutations whereas SL1 had two to five mutations.” These molecular mutations occur because of change in the allele, which leads the virus to express different traits that aid it in surviving within the human body. These traits simply improve its survival, not its virulence. It is very important that we differentiate between a change in the gene sequence and proteins of the Ebola virus, and a functional change of the proteins and genes in the Ebola virus, which would be a change in the impacts and symptoms the Ebola virus would express.
Observation of the increased survivability of the virus, leads us to examine its pathogenesis. In examining the pathogenesis of the virus in human and non-human species, it is clear the virus has evolved genetically, as the strains of the zoonotic disease has greater virulence in human species compared to non-human species. This ease of transmission and higher virulence from animals to humans demonstrate a sustained reassortment of genes in the Ebola virus. This gives more evidence to the conclusion that studying the genetic changes and pathogenesis of the Ebolavirus is a more efficient way to create an Ebola vaccine. According to Ilhem Messaoudi et al, in the published article “Filovirus pathogenesis and immune evasion: insights from Ebola virus and Marburg virus”, the Ebola virus of the Filovirus family has developed five species, the “Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV), Bundibugyo ebolavirus (BDBV), Tai Forrest ebolavirus (TAFV) and Reston ebolavirus (RESTV)” , and they all experience greater success in human species except (RESTV),which has not harmed infected humans because it is highly weakened in humans. In fact, Ebola does not affect the reservoir host (the fruit bat) or “experimentally-infected guinea pigs and mice.” The peculiarity of this phenomenon lies in the structure of filoviruses and how they respond to Interferon Type 1 in the human body. In other words, the viral proteins that structure Ebola and how they respond to Interferon Type 1. As mentioned in both Olabode’s and Messaoudi’s research, they are “seven EBOV proteins” and “these encode seven viral structural proteins known as nucleoprotein (NP), viral protein (VP) 35, VP40, glycoprotein (GP), VP30, VP24, and the large protein (L).” To combat these proteins, the human body has Interferon Type 1 (IFN), – a large subgroup of interferon proteins that help regulate the immune system. This is also in mice.
Analysis of the relationship of Interferon Type I with the viral proteins serves as a guide for the framework of an Ebola vaccine. According to “Tackling Ebola: new insights into prophylactic and therapeutic intervention strategies”, “Antisense therapies, in which oligonucleotides inhibit viral replication, have shown promising results in non-human primates following post-exposure treatment,” and “vaccine research in non-human primates… has produced several promising candidates.” The reasons as to why the virus is successfully fatal in humans is due to how it adapts and manipulates interferon Type 1. For example, as said by the Messaoudi’s article, “the mucin domain of GP shields epitopes”, so they cannot be recognized by antibodies, and hides “histocompatibility complex I molecules, thereby impairing antigen presentation by the host cell.” As for VP24 and NP, they counteract the IFN-induced immune response in Guinea pigs and mice. For in vitro experiments, NP does the same while “VP24 prevents IFN-α/β-induced gene expression and counteracts the antiviral effects of IFN-β by interacting with karyopherin-α1 (also known as importin-α)” – which is “a class of adaptor proteins that are involved in the import of proteins into the cell nucleus.”
It should be acknowledged that a). The zoonotic Ebolavirus disease is not exhibiting new symptoms in human and non-human species, and b0. As a member of the filovirus family it evolves rapidly and therefore has many strains which impedes vaccination and c). Evolution of genes and higher virulence of the virus is due to genetic drift, not functional evolution. With this information on the current observations and varying levels of success in living and in vitro cell cultures, it is incumbent to conclude that analysis of the genetic changes, pathogenesis and study of epidemiological factors in the Ebola virus is the most efficient and logical way to arrive at an appropriate Ebola vaccine. Support of studies that are based on these observations must be prioritized if we are to eliminate the pandemic that is Ebola and contain members of the filovirus family.

Works Cited
“Definition of Interferon.” MedicineNet, www.medicinenet.com/script/main/art.asp?articlekey=3992.
Holland, John, Etsteban Domingo. “Origin and Evolution of Viruses.” Virus Genes, vol 16:1, 1998, pp. 13-15.
“Importin.” Wikipedia, Wikimedia Foundation, 30 Apr. 2018, en.wikipedia.org/wiki/Importin.
Messaoudai, IIhem, et al. “Filovirus Pathogenesis and Immune Evasion: Insights from Ebola Virus and Marburg Virus.” Www-Ncbi-Nlm-Nih-Gov.ccny-proxy1.Libr.ccny.cuny.edu, Nat Rev Microbiol, 6 Oct. 2015, www-ncbi-nlm-nih-gov.ccny-proxy1.libr.ccny.cuny.edu/pmc/articles/PMC5201123/.
Olabode, Abayomi S., et al. “Ebolavirus Is Evolving but Not Changing: No Evidence for Functional Change in EBOV from 1976 to the 2014 Outbreak.” Virology, vol. 482, 15 Mar. 2015, pp. 202–204. Virology.
Park, Daniel J., et al. “Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra Leone.” Cell, 18 June 2015, pp. 1516–1518., doi:http://dx.doi.org/10.1016/j.cell.2015.06.007.

Wit, Emmie D., et al. “Tackling Ebola: New Insights into Prophylactic and Therapeutic Intervention Strategies.” Www-Ncbi-Nlm-Nih-Gov.ccny-proxy1.Libr.ccny.cuny.edu, Genome Med, 27 Jan. 2011, www-ncbi-nlm-nih-gov.ccny-proxy1.libr.ccny.cuny.edu/pmc/articles/PMC3092090/.