Possible role of molecular mimicry in pathogenesis of Ebola virus poses challenges in vaccine design

[Emily]

http://inderscience.metapress.com/co...8434p41912827/

Possible role of molecular mimicry in pathogenesis of Ebola virus: implications for a rational vaccine design
Journal International Journal of Biotechnology
Publisher Inderscience Publishers
ISSN 0963-6048 (Print)
1741-5020 (Online)
Subject Biosciences and Bioinformatics and Environment and Sustainable Development
Issue Volume 9, Number 3-4/2007
Pages 332-343
Subject Group Energy and Environment
Online Date Thursday, June 28, 2007
Authors
Amir Z. Maksyutov1, Alexander G. Bachinsky2, Alexander A. Chepurnov3

1State Research Center of Virology and Biotechnology (SRC VB) Vector, Koltsovo, Novosibirsk region 630559, Russia.
2State Research Center of Virology and Biotechnology (SRC VB) Vector, Koltsovo, Novosibirsk region 630559, Russia.
3Institute of Immunology, Siberian branch of Russian Academy of Medical Sciences, Novosibirsk, Russia
Abstract

Ebola Virus (EBOV) presents a challenge for vaccine development because immune correlates of protection in humans are not well known. In earlier studies we developed a concept of local similarity which refers to resemblance of structural patterns of unrelated proteins as a function of their amino acid composition. The search for local similarities between human and EBOV proteins was performed. The resemblance of NP protein of EBOV to vascular endothelial growth factor and its receptor, which play a key role in the regulation of vascular permeability, was identified. A high degree of local similarity of Ebola GP protein with the tactile protein of the T-cell surface was also revealed. The similarity of the Ebola VP24 protein fragment with complement receptor type 1 (CD35 antigen) appears to be correlated with early activation of complement in lethal Ebola fever. This finding supports our prior studies indicating that VP24 determines the difference between lethal and non-lethal strains of EBOV. Several other similarities of potential significance were identified that might play an important role in the aetiology of Ebola-induced disease. In conclusion, local similarities between EBOV and human host proteins may provide a key to rational design of safe and effective filovirus vaccines. Such a vaccine must be free from epitopes that could potentially trigger Ebola-like hemorrhagic fever due to an autoimmune reaction induced by vaccination and other unanticipated adversities.

[foxp3]

Re: Possible role of molecular mimicry in pathogenesis of Ebola virus poses challenges in vaccine design

Immunotolerance generated against this self antigen CD35 antigen ( central rather than peripheral tolerance), would not necessarily be broken, by vaccination, so autoimmunity is not an inevitable outcome. I.e. the immune system is educated not to respond to self and this education is not lost easily, even in the presence of an adjuvant.

I would therefore wonder about the opposite, I.e. a lack of priming immune response to such epitopes as VP24 in the vaccine as the immune system mistakes this epitope as self and won't respond in a protective manner , May even generate regulatory CD4+ T cells rather than a priming response.

Hopefully there will be other more suitable dominant epitopes which will provide good vaccine targets.

Fp