An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection
ABSTRACT Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromi...
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crasmicro:10.1128/jvi.00078-15 2024-05-19T07:49:54+00:00 An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection Zanin, Mark Keck, Zhen-Yong Rainey, G. Jonah Lam, Chia-Ying Kao Boon, Adrianus C. M. Rubrum, Adam Darnell, Daniel Wong, Sook-San Griffin, Yolanda Xia, Jinming Webster, Robert G. Webby, Richard Johnson, Syd Foung, Steven Perlman, S. 2015 http://dx.doi.org/10.1128/jvi.00078-15 https://journals.asm.org/doi/pdf/10.1128/JVI.00078-15 en eng American Society for Microbiology https://journals.asm.org/non-commercial-tdm-license Journal of Virology volume 89, issue 8, page 4549-4561 ISSN 0022-538X 1098-5514 journal-article 2015 crasmicro https://doi.org/10.1128/jvi.00078-15 2024-05-02T06:49:25Z ABSTRACT Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. To produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted H5N1 influenza viruses, we developed two neutralizing monoclonal antibodies and combined them into a single bispecific Fc fusion protein (the Fc dual-affinity retargeting [FcDART] molecule). In mice, a single therapeutic or prophylactic dose of either monoclonal antibody at 2.5 mg/kg of body weight provided 100% protection against challenge with A/Vietnam/1203/04 (H5N1) or the antigenically drifted strain A/Whooper swan/Mongolia/244/05 (H5N1). In ferrets, a single 1-mg/kg prophylactic dose provided 100% protection against A/Vietnam/1203/04 challenge. FcDART was also effective, as a single 2.5-mg/kg therapeutic or prophylactic dose in mice provided 100% protection against A/Vietnam/1203/04 challenge. Antibodies bound to conformational epitopes in antigenic sites on the globular head of the hemagglutinin protein, on the basis of analysis of mutants with antibody escape mutations. While it was possible to generate escape mutants in vitro , they were neutralized by the antibodies in vivo , as mice infected with escape mutants were 100% protected after only a single therapeutic dose of the antibody used to generate the escape mutant in vitro . In summary, we have combined the antigen specificities of two highly efficacious anti-H5N1 influenza virus antibodies into a bispecific FcDART molecule, which represents a strategy to produce broadly neutralizing antibodies that are effective against antigenically diverse influenza viruses. IMPORTANCE Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and are a pandemic threat. A vaccine is available, but other ... Article in Journal/Newspaper Whooper Swan ASM Journals (American Society for Microbiology) Journal of Virology 89 8 4549 4561 |
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English |
description |
ABSTRACT Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. To produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted H5N1 influenza viruses, we developed two neutralizing monoclonal antibodies and combined them into a single bispecific Fc fusion protein (the Fc dual-affinity retargeting [FcDART] molecule). In mice, a single therapeutic or prophylactic dose of either monoclonal antibody at 2.5 mg/kg of body weight provided 100% protection against challenge with A/Vietnam/1203/04 (H5N1) or the antigenically drifted strain A/Whooper swan/Mongolia/244/05 (H5N1). In ferrets, a single 1-mg/kg prophylactic dose provided 100% protection against A/Vietnam/1203/04 challenge. FcDART was also effective, as a single 2.5-mg/kg therapeutic or prophylactic dose in mice provided 100% protection against A/Vietnam/1203/04 challenge. Antibodies bound to conformational epitopes in antigenic sites on the globular head of the hemagglutinin protein, on the basis of analysis of mutants with antibody escape mutations. While it was possible to generate escape mutants in vitro , they were neutralized by the antibodies in vivo , as mice infected with escape mutants were 100% protected after only a single therapeutic dose of the antibody used to generate the escape mutant in vitro . In summary, we have combined the antigen specificities of two highly efficacious anti-H5N1 influenza virus antibodies into a bispecific FcDART molecule, which represents a strategy to produce broadly neutralizing antibodies that are effective against antigenically diverse influenza viruses. IMPORTANCE Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and are a pandemic threat. A vaccine is available, but other ... |
author2 |
Perlman, S. |
format |
Article in Journal/Newspaper |
author |
Zanin, Mark Keck, Zhen-Yong Rainey, G. Jonah Lam, Chia-Ying Kao Boon, Adrianus C. M. Rubrum, Adam Darnell, Daniel Wong, Sook-San Griffin, Yolanda Xia, Jinming Webster, Robert G. Webby, Richard Johnson, Syd Foung, Steven |
spellingShingle |
Zanin, Mark Keck, Zhen-Yong Rainey, G. Jonah Lam, Chia-Ying Kao Boon, Adrianus C. M. Rubrum, Adam Darnell, Daniel Wong, Sook-San Griffin, Yolanda Xia, Jinming Webster, Robert G. Webby, Richard Johnson, Syd Foung, Steven An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection |
author_facet |
Zanin, Mark Keck, Zhen-Yong Rainey, G. Jonah Lam, Chia-Ying Kao Boon, Adrianus C. M. Rubrum, Adam Darnell, Daniel Wong, Sook-San Griffin, Yolanda Xia, Jinming Webster, Robert G. Webby, Richard Johnson, Syd Foung, Steven |
author_sort |
Zanin, Mark |
title |
An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection |
title_short |
An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection |
title_full |
An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection |
title_fullStr |
An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection |
title_full_unstemmed |
An Anti-H5N1 Influenza Virus FcDART Antibody Is a Highly Efficacious Therapeutic Agent and Prophylactic against H5N1 Influenza Virus Infection |
title_sort |
anti-h5n1 influenza virus fcdart antibody is a highly efficacious therapeutic agent and prophylactic against h5n1 influenza virus infection |
publisher |
American Society for Microbiology |
publishDate |
2015 |
url |
http://dx.doi.org/10.1128/jvi.00078-15 https://journals.asm.org/doi/pdf/10.1128/JVI.00078-15 |
genre |
Whooper Swan |
genre_facet |
Whooper Swan |
op_source |
Journal of Virology volume 89, issue 8, page 4549-4561 ISSN 0022-538X 1098-5514 |
op_rights |
https://journals.asm.org/non-commercial-tdm-license |
op_doi |
https://doi.org/10.1128/jvi.00078-15 |
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Journal of Virology |
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89 |
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8 |
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4549 |
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4561 |
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1799468473462554624 |