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Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines

Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way...

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Autores principales: Zhao, Mengsu, Zhai, Yanfang, Zai, Xiaodong, Mao, Yunyun, Hu, Enbo, Wei, Zhaodong, Li, Yan, Li, Kai, Liu, Yanhong, Xu, Junjie, Yu, Rui, Chen, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10248143/
https://www.ncbi.nlm.nih.gov/pubmed/37305410
http://dx.doi.org/10.3389/fcimb.2023.1195314
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author Zhao, Mengsu
Zhai, Yanfang
Zai, Xiaodong
Mao, Yunyun
Hu, Enbo
Wei, Zhaodong
Li, Yan
Li, Kai
Liu, Yanhong
Xu, Junjie
Yu, Rui
Chen, Wei
author_facet Zhao, Mengsu
Zhai, Yanfang
Zai, Xiaodong
Mao, Yunyun
Hu, Enbo
Wei, Zhaodong
Li, Yan
Li, Kai
Liu, Yanhong
Xu, Junjie
Yu, Rui
Chen, Wei
author_sort Zhao, Mengsu
collection PubMed
description Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way to prevent tularemia. However, there are no Food and Drug Administration (FDA)-approved Ft vaccines thus far due to safety concerns. Herein, three membrane proteins of Ft, Tul4, OmpA, and FopA, and a molecular chaperone, DnaK, were identified as potential protective antigens using a multifactor protective antigen platform. Moreover, the recombinant DnaK, FopA, and Tul4 protein vaccines elicited a high level of IgG antibodies but did not protect against challenge. In contrast, protective immunity was elicited by a replication-defective human type 5 adenovirus (Ad5) encoding the Tul4, OmpA, FopA, and DnaK proteins (Ad5-Tul4, Ad5-OmpA, Ad5-FopA, and Ad5-DnaK) after a single immunization, and all Ad5-based vaccines stimulated a Th1-biased immune response. Moreover, intramuscular and intranasal vaccination with Ad5-Tul4 using the prime-boost strategy effectively eliminated Ft lung, spleen and liver colonization and provided nearly 80% protection against intranasal challenge with the Ft live vaccine strain (LVS). Only intramuscular, not intranasal vaccination, with Ad5-Tul4 protected mice from intraperitoneal challenge. This study provides a comprehensive comparison of protective immunity against Ft provided by subunit or adenovirus-vectored vaccines and suggests that mucosal vaccination with Ad5-Tul4 may yield desirable protective efficacy against mucosal infection, while intramuscular vaccination offers greater overall protection against intraperitoneal tularemia.
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spelling pubmed-102481432023-06-09 Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines Zhao, Mengsu Zhai, Yanfang Zai, Xiaodong Mao, Yunyun Hu, Enbo Wei, Zhaodong Li, Yan Li, Kai Liu, Yanhong Xu, Junjie Yu, Rui Chen, Wei Front Cell Infect Microbiol Cellular and Infection Microbiology Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way to prevent tularemia. However, there are no Food and Drug Administration (FDA)-approved Ft vaccines thus far due to safety concerns. Herein, three membrane proteins of Ft, Tul4, OmpA, and FopA, and a molecular chaperone, DnaK, were identified as potential protective antigens using a multifactor protective antigen platform. Moreover, the recombinant DnaK, FopA, and Tul4 protein vaccines elicited a high level of IgG antibodies but did not protect against challenge. In contrast, protective immunity was elicited by a replication-defective human type 5 adenovirus (Ad5) encoding the Tul4, OmpA, FopA, and DnaK proteins (Ad5-Tul4, Ad5-OmpA, Ad5-FopA, and Ad5-DnaK) after a single immunization, and all Ad5-based vaccines stimulated a Th1-biased immune response. Moreover, intramuscular and intranasal vaccination with Ad5-Tul4 using the prime-boost strategy effectively eliminated Ft lung, spleen and liver colonization and provided nearly 80% protection against intranasal challenge with the Ft live vaccine strain (LVS). Only intramuscular, not intranasal vaccination, with Ad5-Tul4 protected mice from intraperitoneal challenge. This study provides a comprehensive comparison of protective immunity against Ft provided by subunit or adenovirus-vectored vaccines and suggests that mucosal vaccination with Ad5-Tul4 may yield desirable protective efficacy against mucosal infection, while intramuscular vaccination offers greater overall protection against intraperitoneal tularemia. Frontiers Media S.A. 2023-05-25 /pmc/articles/PMC10248143/ /pubmed/37305410 http://dx.doi.org/10.3389/fcimb.2023.1195314 Text en Copyright © 2023 Zhao, Zhai, Zai, Mao, Hu, Wei, Li, Li, Liu, Xu, Yu and Chen https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Zhao, Mengsu
Zhai, Yanfang
Zai, Xiaodong
Mao, Yunyun
Hu, Enbo
Wei, Zhaodong
Li, Yan
Li, Kai
Liu, Yanhong
Xu, Junjie
Yu, Rui
Chen, Wei
Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines
title Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines
title_full Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines
title_fullStr Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines
title_full_unstemmed Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines
title_short Comparative evaluation of protective immunity against Francisella tularensis induced by subunit or adenovirus-vectored vaccines
title_sort comparative evaluation of protective immunity against francisella tularensis induced by subunit or adenovirus-vectored vaccines
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10248143/
https://www.ncbi.nlm.nih.gov/pubmed/37305410
http://dx.doi.org/10.3389/fcimb.2023.1195314
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