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Identification of protective epitopes on ebola virus glycoprotein at the single amino acid level by using recombinant vesicular stomatitis viruses.
- Source :
-
Journal of virology [J Virol] 2003 Jan; Vol. 77 (2), pp. 1069-74. - Publication Year :
- 2003
-
Abstract
- Ebola virus causes lethal hemorrhagic fever in humans, but currently there are no effective vaccines or antiviral compounds for this infectious disease. Passive transfer of monoclonal antibodies (MAbs) protects mice from lethal Ebola virus infection (J. A. Wilson, M. Hevey, R. Bakken, S. Guest, M. Bray, A. L. Schmaljohn, and M. K. Hart, Science 287:1664-1666, 2000). However, the epitopes responsible for neutralization have been only partially characterized because some of the MAbs do not recognize the short synthetic peptides used for epitope mapping. To identify the amino acids recognized by neutralizing and protective antibodies, we generated a recombinant vesicular stomatitis virus (VSV) containing the Ebola virus glycoprotein-encoding gene instead of the VSV G protein-encoding gene and used it to select escape variants by growing it in the presence of a MAb (133/3.16 or 226/8.1) that neutralizes the infectivity of the virus. All three variants selected by MAb 133/3.16 contained a single amino acid substitution at amino acid position 549 in the GP2 subunit. By contrast, MAb 226/8.1 selected three different variants containing substitutions at positions 134, 194, and 199 in the GP1 subunit, suggesting that this antibody recognized a conformational epitope. Passive transfer of each of these MAbs completely protected mice from a lethal Ebola virus infection. These data indicate that neutralizing antibody cocktails for passive prophylaxis and therapy of Ebola hemorrhagic fever can reduce the possibility of the emergence of antigenic variants in infected individuals.
- Subjects :
- Amino Acid Sequence
Animals
Antibodies, Monoclonal administration & dosage
Antibodies, Monoclonal immunology
Cell Line
Fluorescent Antibody Technique
Glycoproteins chemistry
Glycoproteins genetics
Humans
Immunization, Passive
Mice
Molecular Sequence Data
Neutralization Tests
Recombination, Genetic
Sequence Homology, Amino Acid
Vesicular stomatitis Indiana virus immunology
Amino Acids chemistry
Epitopes chemistry
Glycoproteins immunology
Vesicular stomatitis Indiana virus genetics
Viral Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0022-538X
- Volume :
- 77
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 12502822
- Full Text :
- https://doi.org/10.1128/jvi.77.2.1069-1074.2003