SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies.
Rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (PEP). However, current PEP relies on polyclonal immune globulin products purified from pooled human (HRIG) or equine (ERIG) plasma that are either in chronic shortage or in association with...
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ftdoajarticles:oai:doaj.org/article:bfa8db820f94464b8b1aaf5dda615483 2023-05-15T15:08:37+02:00 SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. Tzu-Yuan Chao Shiqi Ren Enyun Shen Susan Moore Shou-Feng Zhang Li Chen Charles E Rupprecht Eric Tsao 2017-12-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0006133 https://doaj.org/article/bfa8db820f94464b8b1aaf5dda615483 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5754141?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006133 https://doaj.org/article/bfa8db820f94464b8b1aaf5dda615483 PLoS Neglected Tropical Diseases, Vol 11, Iss 12, p e0006133 (2017) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2017 ftdoajarticles https://doi.org/10.1371/journal.pntd.0006133 2022-12-31T01:39:01Z Rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (PEP). However, current PEP relies on polyclonal immune globulin products purified from pooled human (HRIG) or equine (ERIG) plasma that are either in chronic shortage or in association with safety concerns. Here, we present the development of an antibody cocktail, SYN023, made of two novel monoclonal antibodies (MAb) CTB011 and CTB012 that could serve as safer and more cost-effective alternatives to the current RIG products. Both CTB011 and CTB012 are humanized MAbs that bind to non-overlapping epitopes on the rabies virus (RABV) glycoprotein (G) with sub-nanomolar affinities. Sequence analysis revealed that many of the critical residues in binding are highly conserved across different species of lyssaviruses. When combined at a 1:1 ratio, CTB011/CTB012 exhibited neutralization capabilities equivalent or superior to HRIG against 10 North American street RABV isolates in vitro and 15 prevalent Chinese RABV strains in animal models. Finally, SYN023, at a dosage of 0.03 mg/kg, was able to offer the same degree of protection as standard HRIG administration (20 IU/kg) in Syrian hamsters challenged with a highly virulent bat (Tadarida brasiliensis) RABV variant. Taken together, the high-potency and broad-spectrum neutralization demonstrated by SYN023 make it an effective candidate for human rabies PEP consideration. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 11 12 e0006133 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Tzu-Yuan Chao Shiqi Ren Enyun Shen Susan Moore Shou-Feng Zhang Li Chen Charles E Rupprecht Eric Tsao SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Rabies is a neglected zoonotic disease that is preventable in humans by appropriate post-exposure prophylaxis (PEP). However, current PEP relies on polyclonal immune globulin products purified from pooled human (HRIG) or equine (ERIG) plasma that are either in chronic shortage or in association with safety concerns. Here, we present the development of an antibody cocktail, SYN023, made of two novel monoclonal antibodies (MAb) CTB011 and CTB012 that could serve as safer and more cost-effective alternatives to the current RIG products. Both CTB011 and CTB012 are humanized MAbs that bind to non-overlapping epitopes on the rabies virus (RABV) glycoprotein (G) with sub-nanomolar affinities. Sequence analysis revealed that many of the critical residues in binding are highly conserved across different species of lyssaviruses. When combined at a 1:1 ratio, CTB011/CTB012 exhibited neutralization capabilities equivalent or superior to HRIG against 10 North American street RABV isolates in vitro and 15 prevalent Chinese RABV strains in animal models. Finally, SYN023, at a dosage of 0.03 mg/kg, was able to offer the same degree of protection as standard HRIG administration (20 IU/kg) in Syrian hamsters challenged with a highly virulent bat (Tadarida brasiliensis) RABV variant. Taken together, the high-potency and broad-spectrum neutralization demonstrated by SYN023 make it an effective candidate for human rabies PEP consideration. |
format |
Article in Journal/Newspaper |
author |
Tzu-Yuan Chao Shiqi Ren Enyun Shen Susan Moore Shou-Feng Zhang Li Chen Charles E Rupprecht Eric Tsao |
author_facet |
Tzu-Yuan Chao Shiqi Ren Enyun Shen Susan Moore Shou-Feng Zhang Li Chen Charles E Rupprecht Eric Tsao |
author_sort |
Tzu-Yuan Chao |
title |
SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
title_short |
SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
title_full |
SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
title_fullStr |
SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
title_full_unstemmed |
SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
title_sort |
syn023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2017 |
url |
https://doi.org/10.1371/journal.pntd.0006133 https://doaj.org/article/bfa8db820f94464b8b1aaf5dda615483 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 11, Iss 12, p e0006133 (2017) |
op_relation |
http://europepmc.org/articles/PMC5754141?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0006133 https://doaj.org/article/bfa8db820f94464b8b1aaf5dda615483 |
op_doi |
https://doi.org/10.1371/journal.pntd.0006133 |
container_title |
PLOS Neglected Tropical Diseases |
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11 |
container_issue |
12 |
container_start_page |
e0006133 |
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1766339940629610496 |