Lambda display phage as a mucosal vaccine delivery vehicle for peptide antigens

González-Cano, Patricia; Gamage, Lakshman N.A.; Marciniuk, Kristen; Hayes, Connie; Napper, Scott; Hayes, Sidney; Griebel, Philip

doi:10.1016/j.vaccine.2017.11.010

Cited by 22 publications

(21 citation statements)

References 42 publications

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“…Examples of decoration proteins used for vaccine development include gpD (λ), which when fused to fragments of the Circovirus 2 capsid protein forms the basis of a λ phage livestock vaccine for pigs [ 136 ]. In a second example, gpD (λ) fused to a prion protein from deer-stimulated production of IgA antibodies in a mouse model without the use of adjuvant [ 137 ]. VNPs displaying gpD (λ) fused to GP2, a peptide derivative from the overexpressed tumor protein HER2/nue, generated a strong cytotoxic T lymphocyte response that had anti-tumor activity when given prophylactically or therapeutically in a mouse model [ 138 ].…”

Section: Nanotechnology Applicationsmentioning

confidence: 99%

Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins

Dedeo

Teschke

Alexandrescu

2020

Viruses

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Decoration proteins are viral accessory gene products that adorn the surfaces of some phages and viral capsids, particularly tailed dsDNA phages. These proteins often play a “cementing” role, reinforcing capsids against accumulating internal pressure due to genome packaging, or environmental insults such as extremes of temperature or pH. Many decoration proteins serve alternative functions, including target cell recognition, participation in viral assembly, capsid size determination, or modulation of host gene expression. Examples that currently have structures characterized to high-resolution fall into five main folding motifs: β-tulip, β-tadpole, OB-fold, Ig-like, and a rare knotted α-helical fold. Most of these folding motifs have structure homologs in virus and target cell proteins, suggesting horizontal gene transfer was important in their evolution. Oligomerization states of decoration proteins range from monomers to trimers, with the latter most typical. Decoration proteins bind to a variety of loci on capsids that include icosahedral 2-, 3-, and 5-fold symmetry axes, as well as pseudo-symmetry sites. These binding sites often correspond to “weak points” on the capsid lattice. Because of their unique abilities to bind virus surfaces noncovalently, decoration proteins are increasingly exploited for technology, with uses including phage display, viral functionalization, vaccination, and improved nanoparticle design for imaging and drug delivery. These applications will undoubtedly benefit from further advances in our understanding of these versatile augmenters of viral functions.

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Section: Nanotechnology Applicationsmentioning

confidence: 99%

Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins

Dedeo

Teschke

Alexandrescu

2020

Viruses

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“…Although both the NH2- and COOH-termini could be used for fusion of antigen peptides [28, 31, 161], the apparent interaction of the NH2-terminus with gpE makes it less desirable [162]. Thus, the COOH-terminus is mainly used for peptide/protein display [163, 164]. Gamage et al showed that λ phage VLPs displaying four immunodominant regions of porcine circovirus 2 capsid protein through fusion to the COOH-terminus of gpD elicited humoral as well as cellular immune responses in pigs [164].…”

Section: Other Bacteriophagesmentioning

confidence: 99%

Bacteriophage T4 nanoparticles for vaccine delivery against infectious diseases

Pan

Zhu

Mahalingam

et al. 2019

Advanced Drug Delivery Reviews

103

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Subunit vaccines containing one or more target antigens from pathogenic organisms represent safer alternatives to whole pathogen vaccines. However, the antigens by themselves are not sufficiently immunogenic and require additives known as adjuvants to enhance immunogenicity and protective efficacy. Assembly of the antigens into virus-like nanoparticles (VLPs) is a better approach as it allows presentation of the epitopes in a more native context. The repetitive, symmetrical, and high density display of antigens on the VLPs mimic pathogen-associated molecular patterns seen on bacteria and viruses. The antigens, thus, might be better presented to stimulate host's innate as well as adaptive immune systems thereby eliciting both humoral and cellular immune responses. Bacteriophages such as phage T4 provide excellent platforms to generate the nanoparticle vaccines. The T4 capsid containing two non-essential outer proteins Soc and Hoc allow high density array of antigen epitopes in the form of peptides, domains, full-length proteins, or even multi-subunit complexes. Co-delivery of DNAs, targeting molecules, and/or molecular adjuvants provides additional advantages. Recent studies demonstrate that the phage T4 VLPs are highly immunogenic, do not need an adjuvant, and provide complete protection against bacterial and viral pathogens. Thus, phage T4 could potentially be developed as a "universal" VLP platform to design future multivalent vaccines against complex and emerging pathogens.

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“…Since gp10B is not essential for assembly of the capsid, it has been explored for antigen display at the C-terminus with small peptides in high copy numbers, or larger proteins with low to mid copy numbers. 41,42 Additionally, the C-terminus of the pV tail protein can be utilized for display, providing an opportunity for fusion of multiple antigens per phage particle. 40 (Table 1).…”

Section: T7 Phagementioning

confidence: 99%

“…In addition, the gpD protein is ideal for antigen display as there are up to 420 copies on the phage and both the N-and C-termini are available for fusion. 41,42 Additionally, the C-terminus of the pV tail protein can be utilized for display, providing an opportunity for fusion of multiple antigens per phage particle.…”

Section: T7 Phagementioning

confidence: 99%

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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Lambda display phage as a mucosal vaccine delivery vehicle for peptide antigens

Cited by 22 publications

References 42 publications

Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins

Keeping It Together: Structures, Functions, and Applications of Viral Decoration Proteins

Bacteriophage T4 nanoparticles for vaccine delivery against infectious diseases

Phage display as a tool for vaccine and immunotherapy development

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