The strong positive correlation between effective affinity and infectivity neutralization of highly cross-reactive monoclonal antibody IIB4, which recognizes antigenic site B on influenza A virus haemagglutinin
| Autor: | F Kostolanský, Gustáv Russ, V Mucha, Stephen A. Wharton, E. Varečková, Tatiana Betakova |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.drug_class
Molecular Sequence Data Antibody Affinity Hemagglutinin Glycoproteins Influenza Virus Cross Reactions Biology Antibodies Viral medicine.disease_cause Monoclonal antibody Microbiology Neutralization Epitope Epitopes Antigen Influenza A virus medicine Animals Amino Acid Sequence Infectivity Antibodies Monoclonal Virology Molecular biology Titer biology.protein Antibody Chickens |
| Zdroj: | Microbiology. 81:1727-1735 |
| ISSN: | 1465-2080 1350-0872 |
| DOI: | 10.1099/0022-1317-81-7-1727 |
| Popis: | Monoclonal antibody (MAb) IIB4 displays a rare combination of virus neutralization (VN) activity and broad cross-reactivity with influenza A virus strains of the H3 subtype isolated in a period from 1973 to 1988. The epitope of this antibody has been identified as around HA1 residues 198, 199 and 201. Here we report that residues 155, 159, 188, 189 and 193 also influence the binding of this antibody. We have used this antibody to study the relationship between antibody affinity and VN activity. Using one MAb and a single epitope on the haemagglutinin (HA) of different influenza viruses we found a strong positive correlation between effective affinity and VN activity of MAb IIB4. A 10-fold increase in effective affinity corresponded to the 2000-fold increase in VN titre. It follows from the law of mass action that for an effective affinityK=9×108 l/mol, 50% VN was achieved at approx. 10% occupation of HA spikes with antibody. In contrast, for an effective affinityK=6×107 l/mol, to achieve 50% VN, occupation of up to 98% of HA spikes was required. An effective affinity aboutK=6×107l/mol thus represents the limiting value for VN because a further decrease in the affinity cannot be compensated by a higher concentration of antibody. |
| Databáze: | OpenAIRE |
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