Challenges
The development of an effective therapeutic vaccine against Ebola given the poorly understood correlates of immunity.
Recommendation: Since the viral sequences for both Ebola and Marburg are known, the use of bioinformatics to both identify epitopes presented in the context of MHC molecules, with a particular focus on MHC Class-I motifs, and to find possible conserved regions among the two viruses. This approach may prove particularly helpful in developing a DNA based-vaccine that will help not only in Ebola outbreaks, but potentially in Marburg outbreaks as well. The animal models to be tested should be non-human primates since they most likely resemble viral infection and progression as in humans. Several vaccination schedules and approaches should be tested including naked DNA vaccination suing INF-a as possible adjuvant followed by an adenoviral vector boost. |
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Easy entry of viral particles inside endothelial cells, macrophages and monocytes thereby halting an appropriate humoral and adaptive response.
Recommendation: Identification of the protein or complexes responsible for viral anchorage and entrance inside the cell. This will help in the identification of an antagonist that will block the entry process. Achievement of the identification of the viral (s) component (s) that facilitates cell infection may include designing Ebola mutants deficient or defective in certain protein components such as the viral glycoprotein or the type I transmembrane protein and test the ability of these mutants to infect target cells.
It is uncertain whether whether the attenuated murine virus is more sensitive to neutralization than wild-type virus. Thus the relative potency of NP, or its requirement of as an immunogen for providing long-term protection remains uncertain.
The use of human adenoviruses as vaccine vectors is problematic because pre-existing immunity in the human population might eventually limit the efficacy of this approach. However, Sullivan et al in 2000 has shown the efficacy of such an approach for protection against EBOV in cynomolgus macaques.
Phase III clinical trials in humans will be difficult to conduct for any EBOV vaccine, because of the sporadic nature of the outbreaks and the potential difficulty in obtaining ethical approvals.
It is imperative that the natural reservoir for Ebola be found. This will give us a more thorough understanding of the transmission route into the human population, potentially giving us insight into what behavior increases or decreases an individual’s risk of contracting the disease. This may also provide additional research approaches to finding a vaccine.
A greater understanding of the environmental conditions that favor an outbreak, thereby allowing the proper authorities to be better able to deploy resources to control an outbreak once it has begun.
Educating indigenous populations to change their behavior in order to lessen the risk of infection by Ebola will be difficult, both on practical and ethical grounds.
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This page last updated: 14 April 2004.
