Abstract:

Ebola hemorrhagic fever is an exceptionally fatal disease in humans, up to 90% lethality when caused by the most virulent strains of Ebola virus.  A recent Ebola epidemic occurred in West Africa from 2013 to 2016 and included nearly 30,000 infected persons, with over 11,000 confirmed deaths.  Ebola virus carries an antisense single-stranded RNA (-ssRNA) genome that is 19 kb in size and encodes just 7 viral proteins.  Infectious Ebola virions are enveloped and adhere to target human cells via viral glycoprotein (GP) interactions with a wide variety of human target proteins, including human folate receptor alpha, (Beta)1 integrins, TYRO3 receptor tyrosine kinases, T-cell immunoglobulin, mucin domain 1 (TIM1), and various lectins (DC-SIGN, L-SIGN, & hMGL).  The promiscuous binding of Ebola GP to such a wide landscape of human receptor proteins might explain how the virus is so capable of infecting a wide array of human cell types.  Entry into the cell occurs via either macropinocytosis, clathrin-mediated endocytosis, or caveolin-mediated endocytosis.  Currently, there are three globally approved Ebola vaccines, with six others in various stages of development.  In 2019, the US Food and Drug Administration authorized use of Ervebo, a recombinant vesicular stomatitis virus (VSV)-based vaccine that expresses the full-length GP from Ebola virus.  Ervebo exhibits an effectiveness of 97.5% at blocking Ebola transmission compared to non-vaccinated persons and has been used effectively in the 2018 Ebola outbreak in the Democratic Republic of the Congo.  Zabdeno/Mvabea is a two-shot vaccine, that consists of a human adenovirus expressing Ebola GP (Zabdeno) while Mvabea uses a modified, attenuated poxvirus.  Ad5-EBOV is a third approved vaccine that also employs a human adenovirus expressing Ebola GP.  All three vaccines help vaccinated individuals generate neutralizing antibodies against the Ebola GP, effectively preventing viral entry and subsequent infection.  Here we showcase our own RNA vaccine design using evolutionarily conserved peptide sequences derived from reference sequence submissions of Ebola variants into NCBI.  We additionally check for potential host anaphylaxis by blasting against the human proteome.  The advantage of RNA vaccine design is that they are purely synthetic and can be rapidly re-formulated to adjust to mutations that occur in the midst of an Ebola pandemic.


 

Team Members

Gwendolyn Ciletti-Dougheri |  (Gary Vanderlaan) |  (Matthew Gacura) | Gannon University

 

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