Self-Assembling Nanoparticles Usher in a New Era of Vaccine Design

We introduce here a mathematical procedure for the structural classification of a specific class of self-assembling protein nanoparticles (SAPNs) that are used as a platform for repetitive antigen display systems. These SAPNs have distinctive geometries as a consequence of the fact that their peptide building blocks are formed from two linked coiled coils that are designed to assemble into trimeric and pentameric clusters. This allows a mathematical description of particle architectures in terms of bipartite (3,5)-regular graphs. Exploiting the relation with fullerene graphs, we provide a complete atlas of SAPN morphologies. The classification enables a detailed understanding of the spectrum of possible particle geometries that can arise in the self-assembly process. Moreover, it provides a toolkit for a systematic exploitation of SAPNs in bioengineering in the context of vaccine design, predicting the density of B-cell epitopes on the SAPN surface, which is critical for a strong humoral immune response.

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Charting a new era in vaccine design

Trends in Immunology ◽

10.1016/s1471-4906(01)02117-2 ◽

2002 ◽

Vol 23 (3) ◽

pp. 166-167

Author(s):

James S Huston

Keyword(s):

Vaccine Design ◽

New Era

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MHC-based vaccination approaches: progress and perspectives

Expert Reviews in Molecular Medicine ◽

10.1017/s1462399403005957 ◽

2003 ◽

Vol 5 (7) ◽

pp. 1-17 ◽

Cited By ~ 10

Author(s):

Narinder K. Mehra ◽

Gurvinder Kaur

Keyword(s):

Geographical Location ◽

Human Leukocyte ◽

Vaccine Design ◽

Hla Class I ◽

Hiv Infections ◽

Distribution Patterns ◽

New Era ◽

Geographical Population ◽

Extended Haplotypes ◽

Fast Progression

The major histocompatibility complex (MHC) harbours genes whose primary function in regulating immune responsiveness to infection is to present foreign antigens to cytotoxic T lymphocytes (CTLs) and T helper cells. In the case of infection by human immunodeficiency virus (HIV), defining the optimal HIV epitopes that are recognised by CTLs is important for vaccine design, and this in turn will depend on the characteristics of the predominant infecting virus. Moreover, the particular MHC human leukocyte antigens (HLAs) expressed by a geographical population is important since these are likely to determine which HIV epitopes are immunodominant in the anti-HIV immune response. Consideration of these aspects has lead to the dawn of a new era of MHC-based vaccine design, in which the CTL epitopes are selected on the basis of the frequency of restricting MHC alleles. This article reviews data on the distribution patterns of molecular subtypes of HLA class I and class II extended haplotypes, discussing distribution among Asian Indians but with reference to global distributions. These data provide a genetic basis for the possible predisposition and fast progression of HIV infections in the Indian population. Since there is selective predominance of different HLA alleles and haplotypes in different populations, a dedicated screening effort is required at the global level to develop MHC-based vaccines against infectious diseases. It is hoped that this might lead to the development of multivalent, poly-epitope, subtype-specific HIV vaccines that are specific for the target geographical location.

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Emerging self-assembling peptide nanomaterial for anti-cancer therapy

Journal of Biomaterials Applications ◽

10.1177/08853282211027882 ◽

2021 ◽

pp. 088532822110278

Author(s):

Lisheng Zhu ◽

Yangyang Shi ◽

Ying Xiong ◽

Li Ba ◽

Qiuting Li ◽

...

Keyword(s):

Immune Escape ◽

Vaccine Design ◽

Resistant Cell ◽

New Drugs ◽

Multi Drug Resistance ◽

Independent Manner ◽

Self Assembling ◽

Specific Proteins ◽

Functional Peptide ◽

Historical Transition

Recently it is mainly focused on anti-tumor comprehensive treatments like finding target tumor cells or activating immune cells to inhibit tumor recurrence and metastasis. At present, chemotherapy and molecular-targeted drugs can inhibit tumor cell growth to a certain extent. However, multi-drug resistance and immune escape often make it difficult for new drugs to achieve expected effects. Peptide hydrogel nanoparticles is a new type of biological material with functional peptide chains as the core and self-assembling peptide (SAP) as the framework. It has a variety of significant biological functions, including effective local inflammation suppression and non-drug-resistant cell killing. Besides, it can induce immune activation more persistently in an adjuvant independent manner when compared with simple peptides. Thus, SAP nanomaterial has great potential in regulating cell physiological functions, drug delivery and sensitization, vaccine design and immunotherapy. Not only that, it is also a potential way to focus on some specific proteins and cells through peptides, which has already been examined in previous research. A full understanding of the function and application of SAP nanoparticles can provide a simple and practical strategy for the development of anti-tumor drugs and vaccine design, which contributes to the historical transition of peptide nanohydrogels from bench to bedside and brings as much survival benefits as possible to cancer patients.

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Developing A Programmable, Self-Assembling Squash Leaf Curl China Virus (SLCCNV) Capsid Proteins Into “Nano-Cargo”-Like Architecture: A Next-Generation “Nanotool” For Biomedical Applications

10.1101/338269 ◽

2018 ◽

Author(s):

Raja Muthuramalingam Thangavelu ◽

Deepan Sundarajan ◽

S.U Mohammed Riyaz ◽

Michael Immanuel Jesse Denison ◽

Dharanivasan Gunasekaran ◽

...

Keyword(s):

Self Assembly ◽

Biomedical Applications ◽

Expression System ◽

Next Generation ◽

New Era ◽

High Profile ◽

Self Assembling ◽

Assembly Kinetics ◽

Leaf Curl

AbstractA new era has begun in which pathogens have become useful scaffolds for nanotechnology applications. In this research/study, an attempt has been made to generate an empty cargo-like architecture from a high-profile plant pathogen of Squash leaf curl China virus (SLCCNV). In this approach, SLCCNV coat protein monomers are obtained efficiently by using a yeast Pichia pastoris expression system. Further, dialysis of purified SLCCNV-CP monomers against various pH strengthenened (5–10) disassembly and assembly buffers produced a self-assembled “Nanocargo”-like architecture, which also exhibited an ability to encapsulate the magnetic nanoparticles at in vitro. Bioinformatics tools were also utilized to predict the possible self-assembly kinetics and bioconjugation sites as well. The biocompatibility of “SLCNNV-CP-Nanocargo” particles was also evaluated by in vitro cancer cells, which eventually proved the particles to be versatile material for the next generation “nanotool” capable of housing various therapeutic or imaging agents.

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A New Era in Vaccine Technology: mRNA-Based Vaccine Design

Journal of Molecular Virology and Immunology ◽

10.46683/jmvi.2020.15 ◽

2021 ◽

Vol 1 (3) ◽

pp. 9-17

Author(s):

Fatih Şahiner ◽

İsmail Selçuk Aygar

Keyword(s):

Vaccine Design ◽

New Era

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Unbiased estimation of particle number and sizes using the new stereological tools: the disector, the fractionator, the selector, and the nucleator — or just point-sampled intercepts

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100104200 ◽

1988 ◽

Vol 46 ◽

pp. 428-429

Author(s):

H.J.G. Gundersen

Keyword(s):

Particle Number ◽

Small Distance ◽

Parallel Plane ◽

Unbiased Estimation ◽

Severe Problem ◽

New Era ◽

Size And Shape ◽

Distinct Property ◽

Sectioned Tissue

Previously, all stereological estimation of particle number and sizes were based on models and notoriously gave biased results, were very inefficient to use and difficult to justify. For all references to old methods and a direct comparison with unbiased methods see recent reviews.The publication in 1984 of the DISECTOR, the first unbiased stereological probe for sampling and counting 3—D objects irrespective of their size and shape, signalled the new era in stereology — and give rise to a number of remarkably simple and efficient techniques based on its distinct property: It is the only known way to obtain an unbiased sample of 3-D objects (cells, organelles, etc). The principle is simple: within a 2-D unbiased frame count or sample only cells which are not hit by a parallel plane at a known, small distance h.The area of the frame and h must be known, which might sometimes in itself be a problem, albeit usually a small one. A more severe problem may arise because these constants are known at the scale of the fixed, embedded and sectioned tissue which is often shrunken considerably.

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Drug Induced Changes in Cell Organelles

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100100299 ◽

1968 ◽

Vol 26 ◽

pp. 110-111

Author(s):

Sarah A. Luse

Keyword(s):

Clinical Medicine ◽

Cell Organelles ◽

Riboflavin Deficiency ◽

Drug Induced ◽

New Era ◽

Health And Disease ◽

In The Beginning ◽

Cellular Pathology ◽

Induced Changes ◽

The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

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Torus Circumference and Thickness Parameters From a Linear DNA Size Series Suggest How Toruses Self-Assemble

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100119430 ◽

1985 ◽

Vol 43 ◽

pp. 522-523

Author(s):

George C. Ruben ◽

Kenneth A. Marx

Keyword(s):

Tertiary Structure ◽

Dna Complexes ◽

Tertiary Structures ◽

Self Assembling ◽

Double Stranded Dna ◽

Calf Thymus ◽

Dna Organization ◽

Condensed Dna ◽

Dna Size

Certain double stranded DNA bacteriophage and viruses are thought to have their DNA organized into large torus shaped structures. Morphologically, these poorly understood biological DNA tertiary structures resemble spermidine-condensed DNA complexes formed in vitro in the total absence of other macromolecules normally synthesized by the pathogens for the purpose of their own DNA packaging. Therefore, we have studied the tertiary structure of these self-assembling torus shaped spermidine- DNA complexes in a series of reports. Using freeze-etch, low Pt-C metal (10-15Å) replicas, we have visualized the microscopic DNA organization of both calf Thymus( CT) and linear 0X-174 RFII DNA toruses. In these structures DNA is circumferentially wound, continuously, around the torus into a semi-crystalline, hexagonal packed array of parallel DNA helix sections.

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