Reformatting palivizumab and motavizumab from IgG to human IgA impairs their efficacy against RSV infection in vitro and in vivo
| Autor: | Daan Augustijn, Karli R. Reiding, C. Erik Hack, Louis J. Bont, Maaike Nederend, Jeanette H. W. Leusen, Manfred Wuhrer, Frank E. J. Coenjaerts, Shamir R. Jacobino, Jan Meeldijk, J. H. Marco Jansen, J. Frederiek Reijneveld |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Viral/genetics Fc receptor Antibodies Viral Protein Engineering Transgenic Mice Monoclonal Immunology and Allergy Non-U.S. Gov't Inbred BALB C Respiratory Syncytial Virus Infections/drug therapy Mice Inbred BALB C biology Research Support Non-U.S. Gov't RSV Isotype 3. Good health Respiratory Syncytial Viruses Antibody mIgA medicine.drug Palivizumab IgG palivizumab Palivizumab/genetics Immunology Mice Transgenic Respiratory Syncytial Virus Infections Antibodies Monoclonal Humanized Research Support Virus Antibodies Antibodies Viral/genetics Humanized/genetics Cell Line 03 medical and health sciences Motavizumab In vivo Antibodies Monoclonal Humanized/genetics Report medicine Journal Article fusion protein Animals Humans neutralizing antibodies business.industry dIgA Respiratory Syncytial Viruses/immunology Immunoglobulin A 030104 developmental biology motavizumab Immunoglobulin G Immunoglobulin A/genetics biology.protein business Immunoglobulin G/genetics antibody glycosylation sIgA |
| Zdroj: | mAbs, 10(3), 453. Landes Bioscience mAbs mAbs, 10(3), 453-462 |
| ISSN: | 1942-0862 |
| Popis: | Respiratory syncytial virus (RSV) infection is a leading cause of hospitalization and mortality in young children. Protective therapy options are limited. Currently, palivizumab, a monoclonal IgG1 antibody, is the only licensed drug for RSV prophylaxis, although other IgG antibody candidates are being evaluated. However, at the respiratory mucosa, IgA antibodies are most abundant and act as the first line of defense against invading pathogens. Therefore, it would be logical to explore the potential of recombinant human IgA antibodies to protect against viral respiratory infection, but very little research on the topic has been published. Moreover, it is unknown whether human antibodies of the IgA isotype are better suited than those of the IgG isotype as antiviral drugs to combat respiratory infections. To address this, we generated various human IgA antibody formats of palivizumab and motavizumab, two well-characterized human IgG1 anti-RSV antibodies. We evaluated their efficacy to prevent RSV infection in vitro and in vivo and found similar, but somewhat decreased efficacy for different IgA subclasses and formats. Thus, reformatting palivizumab or motavizumab into IgA reduces the antiviral potency of either antibody. Moreover, our results indicate that the efficacy of intranasal IgA prophylaxis against RSV infection in human FcαRI transgenic mice is independent of Fc receptor expression. |
| Databáze: | OpenAIRE |
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