A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague

ABSTRACT Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved...

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Autores principales:	Pan Tao, Marthandan Mahalingam, Jingen Zhu, Mahtab Moayeri, Jian Sha, William S. Lawrence, Stephen H. Leppla, Ashok K. Chopra, Venigalla B. Rao
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	anthrax vaccine bacteriophage T4 biodefense plague vaccine small outer capsid protein vaccine delivery Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8e99a89944ec4a70998d621b245a3deb
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spelling	oai:doaj.org-article:8e99a89944ec4a70998d621b245a3deb2021-11-15T15:58:20ZA Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague10.1128/mBio.01926-182150-7511https://doaj.org/article/8e99a89944ec4a70998d621b245a3deb2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01926-18https://doaj.org/toc/2150-7511ABSTRACT Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved vaccine exists for plague. Here, we report the development of a dual anthrax-plague nanoparticle vaccine employing bacteriophage (phage) T4 as a platform. Using an in vitro assembly system, the 120- by 86-nm heads (capsids) of phage T4 were arrayed with anthrax and plague antigens fused to the small outer capsid protein Soc (9 kDa). The antigens included the anthrax protective antigen (PA) (83 kDa) and the mutated (mut) capsular antigen F1 and the low-calcium-response V antigen of the type 3 secretion system from Y. pestis (F1mutV) (56 kDa). These viral nanoparticles elicited robust anthrax- and plague-specific immune responses and provided complete protection against inhalational anthrax and/or pneumonic plague in three animal challenge models, namely, mice, rats, and rabbits. Protection was demonstrated even when the animals were simultaneously challenged with lethal doses of both anthrax lethal toxin and Y. pestis CO92 bacteria. Unlike the traditional subunit vaccines, the phage T4 vaccine uses a highly stable nanoparticle scaffold, provides multivalency, requires no adjuvant, and elicits broad T-helper 1 and 2 immune responses that are essential for complete clearance of bacteria during infection. Therefore, phage T4 is a unique nanoparticle platform to formulate multivalent vaccines against high-risk pathogens for national preparedness against potential bioterror attacks and emerging infections. IMPORTANCE Following the deadly anthrax attacks of 2001, the Centers for Disease Control and Prevention (CDC) determined that Bacillus anthracis and Yersinia pestis that cause anthrax and plague, respectively, are two Tier 1 select agents that pose the greatest threat to the national security of the United States. Both cause rapid death, in 3 to 6 days, of exposed individuals. We engineered a virus nanoparticle vaccine using bacteriophage T4 by incorporating key antigens of both B. anthracis and Y. pestis into one formulation. Two doses of this vaccine provided complete protection against both inhalational anthrax and pneumonic plague in animal models. This dual anthrax-plague vaccine is a strong candidate for stockpiling against a potential bioterror attack involving either one or both of these biothreat agents. Further, our results establish the T4 nanoparticle as a novel platform to develop multivalent vaccines against pathogens of high public health significance.Pan TaoMarthandan MahalingamJingen ZhuMahtab MoayeriJian ShaWilliam S. LawrenceStephen H. LepplaAshok K. ChopraVenigalla B. RaoAmerican Society for Microbiologyarticleanthrax vaccinebacteriophage T4biodefenseplague vaccinesmall outer capsid proteinvaccine deliveryMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	anthrax vaccine bacteriophage T4 biodefense plague vaccine small outer capsid protein vaccine delivery Microbiology QR1-502
spellingShingle	anthrax vaccine bacteriophage T4 biodefense plague vaccine small outer capsid protein vaccine delivery Microbiology QR1-502 Pan Tao Marthandan Mahalingam Jingen Zhu Mahtab Moayeri Jian Sha William S. Lawrence Stephen H. Leppla Ashok K. Chopra Venigalla B. Rao A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague
description	ABSTRACT Bacillus anthracis and Yersinia pestis, the causative agents of anthrax and plague, respectively, are two of the deadliest pathogenic bacteria that have been used as biological warfare agents. Although Biothrax is a licensed vaccine against anthrax, no Food and Drug Administration-approved vaccine exists for plague. Here, we report the development of a dual anthrax-plague nanoparticle vaccine employing bacteriophage (phage) T4 as a platform. Using an in vitro assembly system, the 120- by 86-nm heads (capsids) of phage T4 were arrayed with anthrax and plague antigens fused to the small outer capsid protein Soc (9 kDa). The antigens included the anthrax protective antigen (PA) (83 kDa) and the mutated (mut) capsular antigen F1 and the low-calcium-response V antigen of the type 3 secretion system from Y. pestis (F1mutV) (56 kDa). These viral nanoparticles elicited robust anthrax- and plague-specific immune responses and provided complete protection against inhalational anthrax and/or pneumonic plague in three animal challenge models, namely, mice, rats, and rabbits. Protection was demonstrated even when the animals were simultaneously challenged with lethal doses of both anthrax lethal toxin and Y. pestis CO92 bacteria. Unlike the traditional subunit vaccines, the phage T4 vaccine uses a highly stable nanoparticle scaffold, provides multivalency, requires no adjuvant, and elicits broad T-helper 1 and 2 immune responses that are essential for complete clearance of bacteria during infection. Therefore, phage T4 is a unique nanoparticle platform to formulate multivalent vaccines against high-risk pathogens for national preparedness against potential bioterror attacks and emerging infections. IMPORTANCE Following the deadly anthrax attacks of 2001, the Centers for Disease Control and Prevention (CDC) determined that Bacillus anthracis and Yersinia pestis that cause anthrax and plague, respectively, are two Tier 1 select agents that pose the greatest threat to the national security of the United States. Both cause rapid death, in 3 to 6 days, of exposed individuals. We engineered a virus nanoparticle vaccine using bacteriophage T4 by incorporating key antigens of both B. anthracis and Y. pestis into one formulation. Two doses of this vaccine provided complete protection against both inhalational anthrax and pneumonic plague in animal models. This dual anthrax-plague vaccine is a strong candidate for stockpiling against a potential bioterror attack involving either one or both of these biothreat agents. Further, our results establish the T4 nanoparticle as a novel platform to develop multivalent vaccines against pathogens of high public health significance.
format	article
author	Pan Tao Marthandan Mahalingam Jingen Zhu Mahtab Moayeri Jian Sha William S. Lawrence Stephen H. Leppla Ashok K. Chopra Venigalla B. Rao
author_facet	Pan Tao Marthandan Mahalingam Jingen Zhu Mahtab Moayeri Jian Sha William S. Lawrence Stephen H. Leppla Ashok K. Chopra Venigalla B. Rao
author_sort	Pan Tao
title	A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague
title_short	A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague
title_full	A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague
title_fullStr	A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague
title_full_unstemmed	A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague
title_sort	bacteriophage t4 nanoparticle-based dual vaccine against anthrax and plague
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/8e99a89944ec4a70998d621b245a3deb
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A Bacteriophage T4 Nanoparticle-Based Dual Vaccine against Anthrax and Plague

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