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

Pan, Tao; Mahalingam, Marthandan; Zhu, Jingen; Moayeri, Mahtab; Sha, Jian; Lawrence, William S.; Leppla, Stephen H.; Chopra, Ashok K.; Rao, Venigalla B.

doi:10.1128/mbio.01926-18

Cited by 70 publications

(78 citation statements)

References 50 publications

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“…67 Three plague pandemics have been documented in human history, and the bacteria has also been employed as a biological warfare agent. 67 Three plague pandemics have been documented in human history, and the bacteria has also been employed as a biological warfare agent.…”

Section: T4 Phagementioning

confidence: 99%

“…In another study, the T4 phage display platform was exploited to induce protective immunity against both anthrax and plague. 67 Three plague pandemics have been documented in human history, and the bacteria has also been employed as a biological warfare agent. 62,68 The "Black Death" resulted in the elimination of up to one third of Europe's population, and parts of the United States are still exposed to the plague-causing bacteria Yersinia pestis each year.…”

Section: T4 Phagementioning

confidence: 99%

“…Adapted with permission67 (a) PA from B. anthracis and F1 and V from Y. pestis were fused to the Soc protein on the T4 phage head.…”

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confidence: 99%

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Phage display as a tool for vaccine and immunotherapy development

Hess

Jewell

2019

Bioengineering & Transla Med

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Bacteriophages, or phages, are viruses that specifically infect bacteria and coopt the cellular machinery to create more phage proteins, eventually resulting in the release of new phage particles. Phages are heavily utilized in bioengineering for applications ranging from tissue engineering scaffolds to immune signal delivery. Of specific interest to vaccines and immunotherapies, phages have demonstrated an ability to activate both the innate and adaptive immune systems. The genome of these viral particles can be harnessed for DNA vaccination, or the surface proteins can be exploited for antigen display. More specifically, genes that encode an antigen of interest can be spliced into the phage genome, allowing antigenic proteins or peptides to be displayed by fusion to phage capsid proteins. Phages therefore present antigens to immune cells in a highly ordered and repetitive manner. This review discusses the use of phage with adjuvanting activity as antigen delivery vehicles for vaccination against infectious disease and cancer. K E Y W O R D S bacteriophage, biomaterials, drug delivery, immunology, nanotechnology, phage display, vaccine 1 | INTRODUCTION Bacteriophages, or phages, are prokaryotic viruses that specifically infect bacteria, and are the most abundant life form on earth. 1 Phages were first discovered in the early 20th century and noted for their antibacterial activity. The practice of administering phages (i.e., phage therapy) to patients suffering from bacterial infections began shortly after their discovery, but was controversial largely due to lack of mechanistic knowledge and variable success rates. In fact, the treatment was largely abandoned upon the discovery of antibiotics. 2 Research in this field was reenergized, however, following the development of phage display systems in 1985. 3 George Smith, a chemist at the University of Missouri, demonstrated fusion of peptides to the outer (i.e., capsid) proteins of phages enabling surface display. This work, for which Smith shared a Nobel Prize in 2018, laid the ground work for affinity selection, epitope mapping, and antibody discovery. Since this time, phages have been an important tool for the bioengineering field, exploited for a range of applications including theranostics, 4 batteries, 5,6 drug delivery, 7 and vaccine development. 1Phages are one of many nanotechnologies being investigated for these applications. This review will focus on the advantages that phages provide to the nanomedicine field, specifically vaccination and immunotherapy. Nanomedicine ranges from diagnostics to treatments and relies on the fields of biomedical and chemical engineering,

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Section: T4 Phagementioning

confidence: 99%

Section: T4 Phagementioning

confidence: 99%

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Phage display as a tool for vaccine and immunotherapy development

Hess

Jewell

2019

Bioengineering & Transla Med

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“…In the United Kingdom, and subsequent to the Ebola outbreak in West Africa, vaccine networks for human and veterinary vaccines have formed to prioritize vaccine efforts in these respective contexts [61], while the Department of Health, together with Innovate UK, has supported R&D of vaccine candidates for the prioritized pathogens [62]. As a result of these global initiatives, a number of candidate vaccines are being developed for emerging bacterial and viral pathogens, examples of which, although by no means exhaustive, are cited here [63][64][65][66][67][68][69][70][71][72][73][74]. WHO reports ongoing global vaccine R&D efforts [75] and also tracks the progress of clinical trials for emerging pathogens [76].…”

Section: Vaccine Requirementsmentioning

confidence: 99%

Vaccines for emerging pathogens: prospects for licensure

Williamson

Westlake

2019

Clinical and Experimental Immunology

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Summary Globally, there are a number of emerging pathogens. For most, there are no licensed vaccines available for human use, although there is ongoing research and development. However, given the extensive and increasing list of emerging pathogens and the investment required to bring vaccines into clinical use, the task is huge. Overlaid on this task is the risk of anti‐microbial resistance (AMR) acquisition by micro‐organisms which can endow a relatively harmless organism with pathogenic potential. Furthermore, climate change also introduces a challenge by causing some of the insect vectors and environmental conditions prevalent in tropical regions to begin to spread out from these traditional areas, thus increasing the risk of migration of zoonotic disease. Vaccination provides a defence against these emerging pathogens. However, vaccines for pathogens which cause severe, but occasional, disease outbreaks in endemic pockets have suffered from a lack of commercial incentive for development to a clinical standard, encompassing Phase III clinical trials for efficacy. An alternative is to develop such vaccines to request US Emergency Use Authorization (EUA), or equivalent status in the United States, Canada and the European Union, making use of a considerable number of regulatory mechanisms that are available prior to licensing. This review covers the status of vaccine development for some of the emerging pathogens, the hurdles that need to be overcome to achieve EUA or an equivalent regional or national status and how these considerations may impact vaccine development for the future, such that a more comprehensive stockpile of promising vaccines can be achieved.

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“…The tailed bacteriophage T4 which infects Escherichia coli bacterium is one of the most well-characterized viruses, an exceptional model system in molecular biology, and a powerful platform for gene, vaccine, and therapeutic molecule delivery [18][19][20] . It consists of a large, prolate, icosahedral capsid (head), 1200-Ålong and 860-Å-wide that encapsidates 172-kbp double-stranded DNA genome.…”

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confidence: 99%

Structural morphing in a symmetry-mismatched viral vertex

et al. 2020

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Large biological structures are assembled from smaller, often symmetric, sub-structures. However, asymmetry among sub-structures is fundamentally important for biological function. An extreme form of asymmetry, a 12-fold-symmetric dodecameric portal complex inserted into a 5-fold-symmetric capsid vertex, is found in numerous icosahedral viruses, including tailed bacteriophages, herpesviruses, and archaeal viruses. This vertex is critical for driving capsid assembly, DNA packaging, tail attachment, and genome ejection. Here, we report the near-atomic in situ structure of the symmetry-mismatched portal vertex from bacteriophage T4. Remarkably, the local structure of portal morphs to compensate for symmetry-mismatch, forming similar interactions in different capsid environments while maintaining strict symmetry in the rest of the structure. This creates a unique and unusually dynamic symmetry-mismatched vertex that is central to building an infectious virion.

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

Cited by 70 publications

References 50 publications

Phage display as a tool for vaccine and immunotherapy development

Phage display as a tool for vaccine and immunotherapy development

Vaccines for emerging pathogens: prospects for licensure

Structural morphing in a symmetry-mismatched viral vertex

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