Antibody responses against wild-type yellow fever virus and the 17D vaccine strain: characterization with human monoclonal antibody fragments and neutralization escape variants
| Autor: | Hervé Zeller, Hans-Dieter Klenk, Jan ter Meulen, Jehanara Korimbocus, Roland E. Kontermann, Stephane Daffis |
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| Rok vydání: | 2005 |
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Molecular Phage display Protein Conformation medicine.drug_class Molecular Sequence Data Biology Antibodies Viral Monoclonal antibody Epitope Virus Neutralization Envelope protein Viral Matrix Proteins Neutralization Tests Neutralizing epitope Virology medicine Humans Immune library Amino Acid Sequence Monoclonal antibody fragments Yellow Fever Vaccine Yellow fever Antibodies Monoclonal Gene Products env Genetic Variation medicine.disease Peptide Fragments Antibody Formation Antibody response biology.protein Immunoglobulin Light Chains Antibody Yellow fever virus Immunoglobulin Heavy Chains Conformational epitope |
| Zdroj: | Virology. 337(2):262-272 |
| ISSN: | 0042-6822 |
| DOI: | 10.1016/j.virol.2005.04.031 |
| Popis: | Human monoclonal antibody fragments neutralizing wild-type and vaccine strains of yellow fever (YF) virus (genotypes West Africa I + II, East/Central Africa, 17D-204-WHO) were generated by repertoire cloning from YF patients. Analysis of virus escape variants identified amino acid (aa) 71 in domain II of the envelope glycoprotein (E) as the most critical residue for neutralization, with aa 153–155 in domain I contributing to the epitope. These data confirm the previous mapping of YFV neutralizing epitopes using mouse monoclonal antibodies but suggest that a conformational epitope could be formed by amino acids from domains I and II opposing each other in the dimeric form of the E protein. While the sera of the YF patients showed up to 10-fold reduced neutralizing activity against the 17D escape variants, sera from 17D vaccinees retained their neutralizing titers. Mutations in this major neutralizing epitope of YFV thus do not seem to carry the risk of immune escape in persons immunized with the YFV-17D vaccine. |
| Databáze: | OpenAIRE |
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