Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

Smallpox (variola virus) is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs) against small...

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Autores principales:	Lindsay Crickard, Tahar Babas, Sidharth Seth, Peter Silvera, Lilia Koriazova, Shane Crotty
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dfc9291f762349f6927efd0481dfcd83
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spelling	oai:doaj.org-article:dfc9291f762349f6927efd0481dfcd832021-11-18T08:10:09ZProtection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.1932-620310.1371/journal.pone.0048706https://doaj.org/article/dfc9291f762349f6927efd0481dfcd832012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23133652/?tool=EBIhttps://doaj.org/toc/1932-6203Smallpox (variola virus) is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs) against smallpox are a conservative approach to this problem, as the licensed human smallpox vaccine (vaccinia virus, VACV) primarily works on the basis of protective antibody responses against smallpox. Fully human mAbs (hmAbs) against vaccinia H3 (H3L) and B5 (B5R), targeting both the mature virion (MV) and extracellular enveloped virion (EV) forms, have been developed as potential therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP) studies examining severe combined immunodeficiency mice (SCID) given a lethal VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection against disease and death than either single hmAb or vaccinia immune globulin (VIG). Post-exposure combination mAb therapy provided significant protection against disease and death, and appeared to fully cure the VACV infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV). In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling smallpox disease in immunocompetent or immunodeficient humans.Lindsay CrickardTahar BabasSidharth SethPeter SilveraLilia KoriazovaShane CrottyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 11, p e48706 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lindsay Crickard Tahar Babas Sidharth Seth Peter Silvera Lilia Koriazova Shane Crotty Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
description	Smallpox (variola virus) is a bioweapon concern. Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential therapeutics that can prevent or treat potentially lethal poxvirus infections in humans. Monoclonal antibodies (mAbs) against smallpox are a conservative approach to this problem, as the licensed human smallpox vaccine (vaccinia virus, VACV) primarily works on the basis of protective antibody responses against smallpox. Fully human mAbs (hmAbs) against vaccinia H3 (H3L) and B5 (B5R), targeting both the mature virion (MV) and extracellular enveloped virion (EV) forms, have been developed as potential therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP) studies examining severe combined immunodeficiency mice (SCID) given a lethal VACV infection. Pre-exposure combination hmAb therapy provided significantly better protection against disease and death than either single hmAb or vaccinia immune globulin (VIG). Post-exposure combination mAb therapy provided significant protection against disease and death, and appeared to fully cure the VACV infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV). In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-infection, or 1 hr and 72 hrs post-infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling smallpox disease in immunocompetent or immunodeficient humans.
format	article
author	Lindsay Crickard Tahar Babas Sidharth Seth Peter Silvera Lilia Koriazova Shane Crotty
author_facet	Lindsay Crickard Tahar Babas Sidharth Seth Peter Silvera Lilia Koriazova Shane Crotty
author_sort	Lindsay Crickard
title	Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
title_short	Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
title_full	Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
title_fullStr	Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
title_full_unstemmed	Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
title_sort	protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/dfc9291f762349f6927efd0481dfcd83
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Protection of rabbits and immunodeficient mice against lethal poxvirus infections by human monoclonal antibodies.

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