Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV

The three encephalitic alphaviruses, namely, the Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV), are classified by the Centers for Disease Control and Prevention (CDC) as biothreat agents. Currently, no licensed medical countermeasures (MCMs) against these viruse...

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Autores principales:	Amanda L. Phelps, Lyn M. O’Brien, David O. Ulaeto, Frederick W. Holtsberg, Grant C. Liao, Robin Douglas, M. Javad Aman, Pamela J. Glass, Crystal L. Moyer, Jane Ennis, Larry Zeitlin, Les P. Nagata, Wei-Gang Hu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	neutralizing antibodies (Nabs) anti-EEEV anti-WEEV in vitro neutralization assay in vivo protective efficacy Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6ec4ebe7d4ff40a28edf02bb0e3756d7
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spelling	oai:doaj.org-article:6ec4ebe7d4ff40a28edf02bb0e3756d72021-11-25T19:13:35ZCross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV10.3390/v131122311999-4915https://doaj.org/article/6ec4ebe7d4ff40a28edf02bb0e3756d72021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2231https://doaj.org/toc/1999-4915The three encephalitic alphaviruses, namely, the Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV), are classified by the Centers for Disease Control and Prevention (CDC) as biothreat agents. Currently, no licensed medical countermeasures (MCMs) against these viruses are available for humans. Neutralizing antibodies (NAbs) are fast-acting and highly effective MCMs for use in both pre- and post-exposure settings against biothreat agents. While significant work has been done to identify anti-VEEV NAbs, less has been done to identify NAbs against EEEV and WEEV. In order to develop anti-EEEV or -WEEV NAbs, mice were immunized using complementary strategies with a variety of different EEEV or WEEV immunogens to maximize the generation of NAbs to each of these viruses. Of the hybridomas generated, three anti-EEEV and seven anti-WEEV monoclonal antibodies were identified with in vitro neutralization activity. The most potent neutralizers (two anti-EEEV NAbs and three anti-WEEV NAbs) were further evaluated for neutralization activity against additional strains of EEEV, a single strain of Madariaga virus (formerly South American EEEV), or WEEV. Of these, G1-2-H4 and G1-4-C3 neutralized all three EEEV strains and the Madariaga virus strain, whereas G8-2-H9 and 12 WA neutralized six out of eight WEEV strains. To determine the protective efficacy of these NAbs, the five most potent neutralizers were evaluated in respective mouse aerosol challenge models. All five NAbs demonstrated various levels of protection when administered at doses of 2.5 mg/kg or 10 mg/kg 24 h before the respective virus exposure via the aerosol route. Of these, anti-EEEV NAb G1-4-C3 and anti-WEEV NAb 8C2 provided 100% protection at both doses and all surviving mice were free of clinical signs throughout the study. Additionally, no virus was detected in the brain 14 days post virus exposure. Taken together, efficacious NAbs were developed that demonstrate the potential for the development of cross-strain antibody-based MCMs against EEEV and WEEV infections.Amanda L. PhelpsLyn M. O’BrienDavid O. UlaetoFrederick W. HoltsbergGrant C. LiaoRobin DouglasM. Javad AmanPamela J. GlassCrystal L. MoyerJane EnnisLarry ZeitlinLes P. NagataWei-Gang HuMDPI AGarticleneutralizing antibodies (Nabs)anti-EEEVanti-WEEVin vitro neutralization assayin vivo protective efficacyMicrobiologyQR1-502ENViruses, Vol 13, Iss 2231, p 2231 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	neutralizing antibodies (Nabs) anti-EEEV anti-WEEV in vitro neutralization assay in vivo protective efficacy Microbiology QR1-502
spellingShingle	neutralizing antibodies (Nabs) anti-EEEV anti-WEEV in vitro neutralization assay in vivo protective efficacy Microbiology QR1-502 Amanda L. Phelps Lyn M. O’Brien David O. Ulaeto Frederick W. Holtsberg Grant C. Liao Robin Douglas M. Javad Aman Pamela J. Glass Crystal L. Moyer Jane Ennis Larry Zeitlin Les P. Nagata Wei-Gang Hu Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV
description	The three encephalitic alphaviruses, namely, the Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV), are classified by the Centers for Disease Control and Prevention (CDC) as biothreat agents. Currently, no licensed medical countermeasures (MCMs) against these viruses are available for humans. Neutralizing antibodies (NAbs) are fast-acting and highly effective MCMs for use in both pre- and post-exposure settings against biothreat agents. While significant work has been done to identify anti-VEEV NAbs, less has been done to identify NAbs against EEEV and WEEV. In order to develop anti-EEEV or -WEEV NAbs, mice were immunized using complementary strategies with a variety of different EEEV or WEEV immunogens to maximize the generation of NAbs to each of these viruses. Of the hybridomas generated, three anti-EEEV and seven anti-WEEV monoclonal antibodies were identified with in vitro neutralization activity. The most potent neutralizers (two anti-EEEV NAbs and three anti-WEEV NAbs) were further evaluated for neutralization activity against additional strains of EEEV, a single strain of Madariaga virus (formerly South American EEEV), or WEEV. Of these, G1-2-H4 and G1-4-C3 neutralized all three EEEV strains and the Madariaga virus strain, whereas G8-2-H9 and 12 WA neutralized six out of eight WEEV strains. To determine the protective efficacy of these NAbs, the five most potent neutralizers were evaluated in respective mouse aerosol challenge models. All five NAbs demonstrated various levels of protection when administered at doses of 2.5 mg/kg or 10 mg/kg 24 h before the respective virus exposure via the aerosol route. Of these, anti-EEEV NAb G1-4-C3 and anti-WEEV NAb 8C2 provided 100% protection at both doses and all surviving mice were free of clinical signs throughout the study. Additionally, no virus was detected in the brain 14 days post virus exposure. Taken together, efficacious NAbs were developed that demonstrate the potential for the development of cross-strain antibody-based MCMs against EEEV and WEEV infections.
format	article
author	Amanda L. Phelps Lyn M. O’Brien David O. Ulaeto Frederick W. Holtsberg Grant C. Liao Robin Douglas M. Javad Aman Pamela J. Glass Crystal L. Moyer Jane Ennis Larry Zeitlin Les P. Nagata Wei-Gang Hu
author_facet	Amanda L. Phelps Lyn M. O’Brien David O. Ulaeto Frederick W. Holtsberg Grant C. Liao Robin Douglas M. Javad Aman Pamela J. Glass Crystal L. Moyer Jane Ennis Larry Zeitlin Les P. Nagata Wei-Gang Hu
author_sort	Amanda L. Phelps
title	Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV
title_short	Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV
title_full	Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV
title_fullStr	Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV
title_full_unstemmed	Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV
title_sort	cross-strain neutralizing and protective monoclonal antibodies against eeev or weev
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/6ec4ebe7d4ff40a28edf02bb0e3756d7
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Cross-Strain Neutralizing and Protective Monoclonal Antibodies against EEEV or WEEV

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