Antibody responses against wild-type yellow fever virus and the 17D vaccine strain: characterization with human monoclonal antibody fragments and neutralization escape variants.
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.
Daffis
Stephane
S
Institut für Virologie, Philipps-Universität, Robert-Koch-Strasse 17, 35037 Marburg, Germany. daffis@mailer.uni-marburg.de
Kontermann
Roland E
RE
Korimbocus
Jehanara
J
Zeller
Hervé
H
Klenk
Hans-Dieter
HD
Ter Meulen
Jan
J
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000235:genetics*; D000914:Antibodies, Viral / Q000032:analysis / Q000737:chemistry / Q000235:genetics*; D000917:Antibody Formation; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology*; D011487:Protein Conformation; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000235:genetics* / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D015686:Gene Products, env; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D010446:Peptide Fragments; D014763:Viral Matrix Proteins; D022341:Yellow Fever Vaccine