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Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis

Francisella tularensis, the causative agent of tularemia, is classified as Tier 1 Select Agent with bioterrorism potential. The efficacy of the only available vaccine, LVS, is uncertain and it is not licensed in the U.S. Previously, by using an approach generally applicable to intracellular pathogen...

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Autores principales: De Pascalis, Roberto, Frey, Blake, Rice, Helen M., Bhargava, Varunika, Wu, Terry H., Peterson, Ross L., Conlan, J. Wayne, Sjöstedt, Anders, Elkins, Karen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385090/
https://www.ncbi.nlm.nih.gov/pubmed/35977964
http://dx.doi.org/10.1038/s41541-022-00506-9
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author De Pascalis, Roberto
Frey, Blake
Rice, Helen M.
Bhargava, Varunika
Wu, Terry H.
Peterson, Ross L.
Conlan, J. Wayne
Sjöstedt, Anders
Elkins, Karen L.
author_facet De Pascalis, Roberto
Frey, Blake
Rice, Helen M.
Bhargava, Varunika
Wu, Terry H.
Peterson, Ross L.
Conlan, J. Wayne
Sjöstedt, Anders
Elkins, Karen L.
author_sort De Pascalis, Roberto
collection PubMed
description Francisella tularensis, the causative agent of tularemia, is classified as Tier 1 Select Agent with bioterrorism potential. The efficacy of the only available vaccine, LVS, is uncertain and it is not licensed in the U.S. Previously, by using an approach generally applicable to intracellular pathogens, we identified working correlates that predict successful vaccination in rodents. Here, we applied these correlates to evaluate a panel of SchuS4-derived live attenuated vaccines, namely SchuS4-ΔclpB, ΔclpB-ΔfupA, ΔclpB-ΔcapB, and ΔclpB-ΔwbtC. We combined in vitro co-cultures to quantify rodent T-cell functions and multivariate regression analyses to predict relative vaccine strength. The predictions were tested by rat vaccination and challenge studies, which demonstrated a clear relationship between the hierarchy of in vitro measurements and in vivo vaccine protection. Thus, these studies demonstrated the potential power a panel of correlates to screen and predict the efficacy of Francisella vaccine candidates, and in vivo studies in Fischer 344 rats confirmed that SchuS4-ΔclpB and ΔclpB-ΔcapB may be better vaccine candidates than LVS.
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spelling pubmed-93850902022-08-18 Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis De Pascalis, Roberto Frey, Blake Rice, Helen M. Bhargava, Varunika Wu, Terry H. Peterson, Ross L. Conlan, J. Wayne Sjöstedt, Anders Elkins, Karen L. NPJ Vaccines Article Francisella tularensis, the causative agent of tularemia, is classified as Tier 1 Select Agent with bioterrorism potential. The efficacy of the only available vaccine, LVS, is uncertain and it is not licensed in the U.S. Previously, by using an approach generally applicable to intracellular pathogens, we identified working correlates that predict successful vaccination in rodents. Here, we applied these correlates to evaluate a panel of SchuS4-derived live attenuated vaccines, namely SchuS4-ΔclpB, ΔclpB-ΔfupA, ΔclpB-ΔcapB, and ΔclpB-ΔwbtC. We combined in vitro co-cultures to quantify rodent T-cell functions and multivariate regression analyses to predict relative vaccine strength. The predictions were tested by rat vaccination and challenge studies, which demonstrated a clear relationship between the hierarchy of in vitro measurements and in vivo vaccine protection. Thus, these studies demonstrated the potential power a panel of correlates to screen and predict the efficacy of Francisella vaccine candidates, and in vivo studies in Fischer 344 rats confirmed that SchuS4-ΔclpB and ΔclpB-ΔcapB may be better vaccine candidates than LVS. Nature Publishing Group UK 2022-08-17 /pmc/articles/PMC9385090/ /pubmed/35977964 http://dx.doi.org/10.1038/s41541-022-00506-9 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
De Pascalis, Roberto
Frey, Blake
Rice, Helen M.
Bhargava, Varunika
Wu, Terry H.
Peterson, Ross L.
Conlan, J. Wayne
Sjöstedt, Anders
Elkins, Karen L.
Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis
title Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis
title_full Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis
title_fullStr Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis
title_full_unstemmed Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis
title_short Working correlates of protection predict SchuS4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, Francisella tularensis
title_sort working correlates of protection predict schus4-derived-vaccine candidates with improved efficacy against an intracellular bacterium, francisella tularensis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9385090/
https://www.ncbi.nlm.nih.gov/pubmed/35977964
http://dx.doi.org/10.1038/s41541-022-00506-9
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