Broadly protective murine monoclonal antibodies against influenza B virus target highly conserved neuraminidase epitopes
| Autor: | Ericka Kirkpatrick, Peter Palese, Benjamin R. tenOever, Fatima Amanat, Veronika Chromikova, Sriram Subramaniam, Teddy John Wohlbold, Jessica Tan, Gene S. Tan, Veronica Falconieri, Kira A. Podolsky, Florian Krammer, Philip Meade |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Hemagglutinin Glycoproteins Influenza Virus Antibodies Viral Applied Microbiology and Biotechnology Epitope Madin Darby Canine Kidney Cells chemistry.chemical_compound Epitopes Mice Sf9 Cells education.field_of_study Mice Inbred BALB C virus diseases Antibodies Monoclonal 3. Good health Female Antibody Microbiology (medical) Oseltamivir medicine.drug_class Immunology Population Neuraminidase Biology Cross Reactions Monoclonal antibody Microbiology Virus Antigenic drift Article 03 medical and health sciences Viral Proteins Dogs Orthomyxoviridae Infections Influenza Human Genetics medicine Animals Humans education Cell Biology Virology Antibodies Neutralizing Disease Models Animal Influenza B virus 030104 developmental biology chemistry biology.protein |
| Zdroj: | Nature microbiology |
| ISSN: | 2058-5276 |
| Popis: | A substantial proportion of influenza-related childhood deaths are due to infection with influenza B viruses, which co-circulate in the human population as two antigenically distinct lineages defined by the immunodominant receptor binding protein, haemagglutinin. While broadly cross-reactive, protective monoclonal antibodies against the haemagglutinin of influenza B viruses have been described, none targeting the neuraminidase, the second most abundant viral glycoprotein, have been reported. Here, we analyse a panel of five murine anti-neuraminidase monoclonal antibodies that demonstrate broad binding, neuraminidase inhibition, in vitro antibody-dependent cell-mediated cytotoxicity and in vivo protection against influenza B viruses belonging to both haemagglutinin lineages and spanning over 70 years of antigenic drift. Electron microscopic analysis of two neuraminidase–antibody complexes shows that the conserved neuraminidase epitopes are located on the head of the molecule and that they are distinct from the enzymatic active site. In the mouse model, one therapeutic dose of antibody 1F2 was more protective than the current standard of treatment, oseltamivir, given twice daily for six days. This study reports the identification of broadly protective antibodies targeting the influenza B neuraminidase away from its active site. One dose of antibody therapy was more protective in mice than multiple doses of the current standard of care. |
| Databáze: | OpenAIRE |
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