Microbial Genetics BT405
Thomas Jefferson University
December 15, 2010
Development of a Monovalent Vaccine Based on cAdVax Technology Against Zaire Ebola Virus Offers Hope in Developing a Bivalent Vaccine Against the 2 Deadliest Strains
Ebola viruses are a group of highly pathogenic filoviruses that cause outbreaks of severe hemorrhagic fever in humans and non-human primates, with a rate of high mortality. This virus was first recognized in The Democratic Republic of Congo in 1976. Since its discovery, it continues to cause outbreaks in equatorial Africa. Ebola virus constitutes an important local public health threat in Africa, with a worldwide effect through imported infections and through the fear of misuse for biological terrorism. A vaccine which is safe and effective is needed because of its continuous emergence. The second challenging issue for an Ebola virus vaccine is to have the ability to protect against infection from aerosolized viruses. This has been a long-time concern, as aerosols are the most likely form for these viruses as a biological threat. This study indicates the potential for developing an effective monovalent Ebola virus vaccine based on the cAdVax technology, which demonstrated effectiveness in protecting against direct infection and aerosolized infection. These results show that it is feasible and of high importance to create an Ebola virus vaccine that would be effective in the event of a natural outbreak or the event of the virus being used as biological threat.
Ebola virus is regarded as the prototype pathogen of viral haemorrhagic fever, causing severe disease and high case fatality rates. This high fatality, combined with the absence of treatment and vaccination options, makes Ebola virus an important public health pathogen and biothreat pathogen. Ebola virus and Marburg virus constitute the family Filoviridae. Filoviruses are enveloped, non-segmented, negative-stranded RNA viruses of varying morphology. These viruses have characteristic filamentous particles that give the virus family its name . The exact origin, locations, and natural reservoir of Ebola virus remain unknown. However, on the basis of available evidence and the nature of similar viruses, researchers believe that the virus is zoonotic with four of the five subtypes occurring in an animal host native to Africa. A similar host, most likely in the Philippines, is probably associated with the Ebola-Reston subtype, which was isolated from infected cynomolgous monkeys that were imported to the United States and Italy from the Philippines. The virus is not known to be native to other continents, such as North America . Ebola forms long filamentous virions inside infected cells. When a virion is made, the structural proteins associate with the RNA strand, packaging it in a capsid that then associates with viral proteins that insert into the cell membrane, which allows the whole package to bud off from the infected cell and form a new virion. The genetic material is a single strand of antisense (-) RNA of about 20,000 nucleotides. When transcribed by its own polymerase enzyme, the viral RNA codes for a nucleoprotein, a few structural proteins, the polymerase, and a glycoprotein . The glycoprotein forms spikes, approximately seven nanometers long, on the virion surface. These glycoproteins define the receptor specificity, mediate the cell fusion and cell entry, and may have certain domains that interfere with other cell functions. Like all viruses, Ebola has a certain cell specificity; it targets endothelial cells and macrophages. Ebola may even use its spikes to spread from cell to cell, thus evading the immune system and increasing its virulence . Which most likely has something to do with its extreme pathogenicity and the fact...