Development of a Modular NTA:His Tag Viral Vaccine for Co-delivery of Antigen and Adjuvant

Chung, Young Hun; Volckaert, Britney A.; Steinmetz, Nicole F.

doi:10.1021/acs.bioconjchem.2c00601

Cited by 9 publications

(5 citation statements)

References 55 publications

(98 reference statements)

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“…The immunization with CPMV/Qβ-S100A9 elicited high antibody titers. The viral nanoparticles (VNPs) act as a carrier and adjuvant, and recent research highlights that in particular, conjugation results in codelivery of the epitope and adjuvant to the same cell boosting the potency of antibody production ( 52 – 55 ).…”

Section: Resultsmentioning

confidence: 99%

Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis

Chung,

Ortega-Rivera,

Volckaert

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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Metastatic cancer accounts for 90% of all cancer-related deaths and continues to be one of the toughest challenges in cancer treatment. A growing body of data indicates that S100A9, a major regulator of inflammation, plays a central role in cancer progression and metastasis, particularly in the lungs, where S100A9 forms a premetastatic niche. Thus, we developed a vaccine against S100A9 derived from plant viruses and virus-like particles. Using multiple tumor mouse models, we demonstrate the effectiveness of the S100A9 vaccine candidates in preventing tumor seeding within the lungs and outgrowth of metastatic disease. The elicited antibodies showed high specificity toward S100A9 without cross-reactivity toward S100A8, another member of the S100A family. When tested in metastatic mouse models of breast cancer and melanoma, the vaccines significantly reduced lung tumor nodules after intravenous challenge or postsurgical removal of the primary tumor. Mechanistically, the vaccines reduce the levels of S100A9 within the lungs and sera, thereby increasing the expression of immunostimulatory cytokines with antitumor function [(interleukin) IL-12 and interferonγ] while reducing levels of immunosuppressive cytokines (IL-10 and transforming growth factorβ). This also correlated with decreased myeloid-derived suppressor cell populations within the lungs. This work has wide-ranging impact, as S100A9 is overexpressed in multiple cancers and linked with poor prognosis in cancer patients. The data presented lay the foundation for the development of therapies and vaccines targeting S100A9 to prevent metastasis.

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Section: Resultsmentioning

confidence: 99%

Viral nanoparticle vaccines against S100A9 reduce lung tumor seeding and metastasis

Chung,

Ortega-Rivera,

Volckaert

et al. 2023

Proc. Natl. Acad. Sci. U.S.A.

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“…To surmount these limitations, they have successfully loaded bacteriophage nanoplatforms. For example, the linkage of 2-methoxyethoxy-8-oxo-9-(4-carboxybenzyl) adenine (1V209) as TLR7 agonist on Qβ has reduced tumor growth in vivo and has extended the survival of mice in comparison to those treated with free 1V209 [165]. To this end, Bachmann et al have demonstrated the incorporation of CpG oligodeoxynucleotide (ODN) into Qβ, which serve as carriers [69].…”

Section: Phage-based Anticancer Vaccines Deliverymentioning

confidence: 99%

Delivery of Therapeutics Using Bacteriophage Vectors

Venkataraman,

Shahgolzari,

Yavari

et al. 2024

Preprint

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Bacteriophages are viruses obligately infecting bacteria. They constitute the most numerous categories of biological forms populating our biosphere and are highly diverse and capable of infecting almost all bacteria. Phages make use of their host cell molecular machinery to express their own genes as they lack the ability to independently reproduce themselves. The inimitable characteristics of bacteriophages have enabled them to become propitious tools in biotechnology and genetic engineering. Phages show no tropism for mammalian cells but however, can be easily modified to present targeting ligands on their surface as coat protein fusions without any negative impacts on phage structure. These displayed ligands thereupon guide the recognition, interaction, and internalization of the phage into cells wherein efficiency of transfection is directly influenced by the copy number of the ligands used for targeting. Engineered phages are more efficacious for transgene delivery and gene expression in cancer cells when compared to other non-viral gene transfer strategies and are therefore being employed in developing cancer vaccines. The high level of stability as well as resistance of bacteriophages to various environmental conditions have enabled the development of virus-like particles (VLPs) capable of successful deliverance of several therapeutic drug cargos into tumors by selective targeting. Phage display technology has been used in therapy of Alzheimer’s disease and drug delivery into the brain. Exogenous peptides fused into the coat protein of phages enables the display of these peptides on the phage surface to generate combinatorial phage that facilitates their rapid separation using their ability to bind to a specific molecular target. Phage therapy has been shown to be safe in clinical settings when compared to antibiotics as it shows no adverse anaphylaxis nor adverse effects such as the emergence of multi-drug resistant bacteria. This review provides intriguing details of the use of natural and engineered phages in the therapy of diseases such as cancer, bacterial infections, bovine mastitis and dementia in addition to the use of CRISPR-Cas9 technology in generating genetically engineered phages. Further, the use of phage display technology in generating monoclonal antibodies against various human diseases is elucidated.

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“…2c). 48 In vivo studies revealed that compared with free agonists or simple mixtures of agonists and VLPs, agonist chemically conjugated to VLPs elicited higher production of inflammatory cytokines, Apart from viruses derived from plant sources, the protein capsid of bacteriophages infecting bacteria has been established as a self-assembly VLP antigen-loading platform. In addition to the bacteriophage Qβ VLPs mentioned above, the P22 VLP derived from the Salmonella typhimurium bacteriophage P22 is considered a versatile VLP platform owing to its outstanding stability, modifiability, and facile heterologous expression.…”

Section: Vlpsmentioning

confidence: 99%

“…[45][46][47] (2) Immune adjuvants: PNPs can carry adjuvants like CpG through covalent interaction and other methods, further activating APCs by means of promoting the maturation of dendritic cells (DCs) and the polarization of tumor-associated macrophage (TAM) into the tumor-suppressing M1 phenotype, also releasing inflammatory cytokines to reverse the immunosuppressive tumor microenvironment. [48][49][50] (3) Drugs/photosensitizers/photothermal agents: due to the hydrophobic interactions of proteins like albumin and the pHresponsive characteristic of ferritin, various cargoes can be loaded into PNPs. For example, loading with chemotherapeutic drugs such as doxorubicin (DOX) and paclitaxel can induce ICD and enhance anti-tumor immune responses, or loading with photosensitizers/photothermal agents for photodynamic therapy (PDT)/photothermal therapy (PTT) also can induce ICD or generate reactive oxygen species (ROS) capable of directly killing cancer cells.…”

Section: Introductionmentioning

confidence: 99%