IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model

The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination...

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Main Authors: M. Shannon Keckler, Johanna S Salzer, Nishi Patel, Michael B Townsend, Yoshinori J Nakazawa, Jeffrey B Doty, Nadia F Gallardo-Romero, Panayampalli S Satheshkumar, Darin S Carroll, Kevin L Karem, Inger K Damon
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/8/3/396
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author M. Shannon Keckler
Johanna S Salzer
Nishi Patel
Michael B Townsend
Yoshinori J Nakazawa
Jeffrey B Doty
Nadia F Gallardo-Romero
Panayampalli S Satheshkumar
Darin S Carroll
Kevin L Karem
Inger K Damon
author_facet M. Shannon Keckler
Johanna S Salzer
Nishi Patel
Michael B Townsend
Yoshinori J Nakazawa
Jeffrey B Doty
Nadia F Gallardo-Romero
Panayampalli S Satheshkumar
Darin S Carroll
Kevin L Karem
Inger K Damon
author_sort M. Shannon Keckler
collection DOAJ
description The protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 10<sup>4</sup> pfu (2× LD<sub>50</sub>) or 10<sup>6</sup> pfu (170× LD<sub>50</sub>) and vaccinated the animals with IMVAMUNE<sup>®</sup> or ACAM2000<sup>®</sup> either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD<sub>50</sub>, but not the 170× LD<sub>5</sub> challenge. In the 2× LD<sub>50</sub> challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE<sup>®</sup>, but ACAM2000<sup>®</sup> was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.
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spelling doaj.art-45feba1fdaaf47beb6d477cf9db7c9cd2023-11-20T07:19:13ZengMDPI AGVaccines2076-393X2020-07-018339610.3390/vaccines8030396IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog ModelM. Shannon Keckler0Johanna S Salzer1Nishi Patel2Michael B Townsend3Yoshinori J Nakazawa4Jeffrey B Doty5Nadia F Gallardo-Romero6Panayampalli S Satheshkumar7Darin S Carroll8Kevin L Karem9Inger K Damon10Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAPoxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Atlanta, GA 30333, USAThe protection provided by smallpox vaccines when used after exposure to Orthopoxviruses is poorly understood. Postexposu re administration of 1st generation smallpox vaccines was effective during eradication. However, historical epidemiological reports and animal studies on postexposure vaccination are difficult to extrapolate to today’s populations, and 2nd and 3rd generation vaccines, developed after eradication, have not been widely tested in postexposure vaccination scenarios. In addition to concerns about preparedness for a potential malevolent reintroduction of variola virus, humans are becoming increasingly exposed to naturally occurring zoonotic orthopoxviruses and, following these exposures, disease severity is worse in individuals who never received smallpox vaccination. This study investigated whether postexposure vaccination of prairie dogs with 2nd and 3rd generation smallpox vaccines was protective against monkeypox disease in four exposure scenarios. We infected animals with monkeypox virus at doses of 10<sup>4</sup> pfu (2× LD<sub>50</sub>) or 10<sup>6</sup> pfu (170× LD<sub>50</sub>) and vaccinated the animals with IMVAMUNE<sup>®</sup> or ACAM2000<sup>®</sup> either 1 or 3 days after challenge. Our results indicated that postexposure vaccination protected the animals to some degree from the 2× LD<sub>50</sub>, but not the 170× LD<sub>5</sub> challenge. In the 2× LD<sub>50</sub> challenge, we also observed that administration of vaccine at 1 day was more effective than administration at 3 days postexposure for IMVAMUNE<sup>®</sup>, but ACAM2000<sup>®</sup> was similarly effective at either postexposure vaccination time-point. The effects of postexposure vaccination and correlations with survival of total and neutralizing antibody responses, protein targets, take formation, weight loss, rash burden, and viral DNA are also presented.https://www.mdpi.com/2076-393X/8/3/396monkeypox viruspostexposure vaccinationsmallpox vaccinesprairie dog model
spellingShingle M. Shannon Keckler
Johanna S Salzer
Nishi Patel
Michael B Townsend
Yoshinori J Nakazawa
Jeffrey B Doty
Nadia F Gallardo-Romero
Panayampalli S Satheshkumar
Darin S Carroll
Kevin L Karem
Inger K Damon
IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
Vaccines
monkeypox virus
postexposure vaccination
smallpox vaccines
prairie dog model
title IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
title_full IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
title_fullStr IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
title_full_unstemmed IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
title_short IMVAMUNE<sup>®</sup> and ACAM2000<sup>®</sup> Provide Different Protection against Disease When Administered Postexposure in an Intranasal Monkeypox Challenge Prairie Dog Model
title_sort imvamune sup r sup and acam2000 sup r sup provide different protection against disease when administered postexposure in an intranasal monkeypox challenge prairie dog model
topic monkeypox virus
postexposure vaccination
smallpox vaccines
prairie dog model
url https://www.mdpi.com/2076-393X/8/3/396
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