Passive immunization with an extended half-life monoclonal antibody protects Rhesus macaques against aerosolized ricin toxin.

NPJ Vaccines
Chad J RoyNicholas J Mantis

Abstract

Inhalation of ricin toxin (RT), a Category B biothreat agent, provokes an acute respiratory distress syndrome marked by pro-inflammatory cytokine and chemokine production, neutrophilic exudate, and pulmonary edema. The severity of RT exposure is attributed to the tropism of the toxin's B subunit (RTB) for alveolar macrophages and airway epithelial cells, coupled with the extraordinarily potent ribosome-inactivating properties of the toxin's enzymatic subunit (RTA). While there are currently no vaccines or treatments approved to prevent RT intoxication, we recently described a humanized anti-RTA IgG1 MAb, huPB10, that was able to rescue non-human primates (NHPs) from lethal dose RT aerosol challenge if administered by intravenous (IV) infusion within hours of toxin exposure. We have now engineered an extended serum half-life variant of that MAb, huPB10-LS, and evaluated it as a pre-exposure prophylactic. Five Rhesus macaques that received a single intravenous infusion (25 mg/kg) of huPB10-LS survived a lethal dose aerosol RT challenge 28 days later, whereas three control animals succumbed to RT intoxication within 48 h. The huPB10-LS treated animals remained clinically normal in the hours and days following toxin insult, suggest...Continue Reading

References

Jun 30, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meghan L LindauerBruce E Magun
Jan 19, 2010·Nature Biotechnology·Jonathan ZalevskyJohn R Desjarlais
Nov 4, 2011·MAbs·Timothy T Kuo, Victoria G Aveson
Nov 30, 2011·MAbs·Jeffrey W FroudePhilippe Thullier
Feb 23, 2013·Human Vaccines & Immunotherapeutics·Daniel N WolfePaula Bryant
Mar 22, 2013·Clinical and Vaccine Immunology : CVI·Joanne M O'HaraNicholas J Mantis
Jan 22, 2014·Nature Reviews. Immunology·Tracy Hussell, Thomas J Bell
Mar 17, 2015·Proceedings of the National Academy of Sciences of the United States of America·Chad J RoyEllen S Vitetta
Jul 4, 2015·Cancer Immunology Research·David J DiLillo, Jeffrey V Ravetch
Jul 29, 2016·Clinical and Vaccine Immunology : CVI·Greta Van SlykeNicholas J Mantis
Nov 29, 2016·Nature Reviews. Immunology·Tim WorbsReinhold Förster
Feb 6, 2018·Military Medicine·Theodore J CieslakUNKNOWN NATO Biological Medical Advisory Panel
Apr 25, 2018·The Journal of Infectious Diseases·Bing YangSamuel K Lai
Sep 3, 2018·Vaccine·Jennifer WestfallNicholas J Mantis
Nov 2, 2018·American Journal of Physiology. Lung Cellular and Molecular Physiology·Anita SapoznikovTamar Sabo
Jan 11, 2019·JCI Insight·Chad J RoyNicholas J Mantis
Apr 12, 2019·Current Opinion in HIV and AIDS·Mar Naranjo-Gomez, Mireia Pelegrin
Jun 21, 2019·Toxins·Natalia Sowa-RogozińskaMonika Słomińska-Wojewódzka

❮ Previous
Next ❯

Citations

Sep 7, 2020·Journal of Immunological Methods·Jennifer DoeringNicholas J Mantis

❮ Previous
Next ❯

Methods Mentioned

BETA
bronchoalveolar lavage
ELISA
biosensors

Software Mentioned

GraphPad
PyMol
R package FactoMineR
GraphPad Prism

Related Concepts

Related Feeds

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.

© 2021 Meta ULC. All rights reserved