Classically all vaccines were produced using live or attenuated microorganisms or parts of them. However, the use of whole organisms, their components or the biological process for vaccine production ...has several weaknesses. The presence of immunologically redundant biological components or biological impurities in such vaccines might cause major problems. All the disadvantageous of traditional vaccines might be overcome
via
the development of fully synthetic peptide-based vaccines. However, once minimal antigenic epitopes only are applied for immunisation, the immune responses are poor. The use of an adjuvant can overcome this obstacle; however, it may raise new glitches. Here we briefly summarise the current stand on peptide-based vaccines, discuss epitope and adjuvant design, and multi-epitope and nanoparticle-based vaccine approaches. This mini review discusses also the disadvantages and benefits associated with peptide-based vaccines. It proposes possible methods to overcome the weaknesses of the synthetic vaccine strategy and suggests future directions for its development.
This review summarise the current stand and future perspective on synthetic peptide-based vaccines.
Traditional vaccines, based on the administration of killed or attenuated microorganisms, have proven to be among the most effective methods for disease prevention. Safety issues related to ...administering these complex mixtures, however, prevent their universal application. Through identification of the microbial components responsible for protective immunity, vaccine formulations can be simplified, enabling molecular-level vaccine characterization, improved safety profiles, prospects to develop new high-priority vaccines (e.g. for HIV, tuberculosis, and malaria), and the opportunity for extensive vaccine component optimization. This subunit approach, however, comes at the expense of decreased immunity, requiring the addition of immunostimulatory agents (adjuvants). As few adjuvants are currently used in licensed vaccines, adjuvant development represents an exciting area for medicinal chemists to play a role in the future of vaccine development. In addition, immune responses can be further customized though optimization of delivery systems, tuning the size of particulate vaccines, targeting specific cells of the immune system (e.g. dendritic cells), and adding components to aid vaccine efficacy in whole immunized populations (e.g. promiscuous T-helper epitopes). Herein we review the current state of the art and future direction in subunit vaccine development, with a focus on the described components and their potential to steer the immune response toward a desired response.
Glycosylation of peptides is a promising strategy for modulating the physicochemical properties of peptide drugs and for improving their absorption through biological membranes. This review ...highlights various methods for the synthesis of glycoconjugates and recent progress in the development of glycosylated peptide therapeutics. Furthermore, the impacts of glycosylation in overcoming the existing barriers that restrict oral and brain delivery of peptides are described herein.
Glycosylation of peptides is a promising strategy for modulating the physicochemical properties of peptide drugs and for improving their absorption through biological membranes.
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•Smaller polymer-peptide conjugates-based nanoparticles are often more immunogenic.•Lipid-antigen conjugates-based nanoparticles can interact with immune receptors.•Peptides with ...β-sheet conformation usually form nanofibers.•α-Helical and random coil peptides tend to self-assemble into nanoparticles.•Peptide-based nanostructures are usually poorer inducers of immune responses.
Peptide based-vaccines are becoming one of the most widely investigated prophylactic and therapeutic health care interventions against a variety of diseases, including cancer. However, the lack of a safe and highly efficient adjuvant (immune stimulant) is regarded as the biggest obstacle to vaccine development. The incorporation of a peptide antigen in a nanostructure-based delivery system was recently shown to overcome this obstacle. Nanostructures are often formed from antigens conjugated to molecules such as polymers, lipids, and peptide, with the help of self-assembly phenomenon. This review describes the application of self-assembly process for the production of peptide-based vaccine candidates and the ability of these nanostructures to stimulate humoral and cellular immune responses.
Since the invention of solid phase synthetic methods by Merrifield in 1963, the number of research groups focusing on peptide synthesis has grown exponentially. However, the original step-by-step ...synthesis had limitations: the purity of the final product decreased with the number of coupling steps. After the development of Boc and Fmoc protecting groups, novel amino acid protecting groups and new techniques were introduced to provide high quality and quantity peptide products. Fragment condensation was a popular method for peptide production in the 1980s, but unfortunately the rate of racemization and reaction difficulties proved less than ideal. Kent and co-workers revolutionized peptide coupling by introducing the chemoselective reaction of unprotected peptides, called native chemical ligation. Subsequently, research has focused on the development of novel ligating techniques including the famous click reaction, ligation of peptide hydrazides, and the recently reported α-ketoacid-hydroxylamine ligations with 5-oxaproline. Several companies have been formed all over the world to prepare high quality Good Manufacturing Practice peptide products on a multi-kilogram scale. This review describes the advances in peptide chemistry including the variety of synthetic peptide methods currently available and the broad application of peptides in medicinal chemistry.
The chemical composition, size, shape and surface characteristics of nanoparticles affect the way proteins bind to these particles, and this in turn influences the way in which nanoparticles interact ...with cells and tissues. Nanomaterials bound with proteins can result in physiological and pathological changes, including macrophage uptake, blood coagulation, protein aggregation and complement activation, but the mechanisms that lead to these changes remain poorly understood. Here, we show that negatively charged poly(acrylic acid)-conjugated gold nanoparticles bind to and induce unfolding of fibrinogen, which promotes interaction with the integrin receptor, Mac-1. Activation of this receptor increases the NF-κB signalling pathway, resulting in the release of inflammatory cytokines. However, not all nanoparticles that bind to fibrinogen demonstrated this effect. Our results show that the binding of certain nanoparticles to fibrinogen in plasma offers an alternative mechanism to the more commonly described role of oxidative stress in the inflammatory response to nanomaterials.
Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable ...in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide "drugs" initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.
The Self-Compassion Scale (SCS) is a widely used measure to assess the trait of self-compassion, and, so far, it has been implicitly assumed that it functions the same way across different groups. ...This assumption needs to be explicitly tested to ascertain that no measurement biases exist. To address this issue, the present study sought to systematically examine the generalizability of the bifactor exploratory structural equation modeling operationalization of the SCS via tests of measurement invariance across a wide range of populations, varying according to features such as student or community status, gender, age, and language. Secondary data were used for this purpose and included a total of 18 samples and 12 different languages (N = 10,997). Multigroup analyses revealed evidence for the configural, weak, strong, strict, and latent variance–covariance of the bifactor exploratory structural equation modeling operationalization of the SCS across different groups. These findings suggest that the SCS provides an assessment of self-compassion that is psychometrically equivalent across groups. However, findings comparing latent mean invariance found that levels of self-compassion differed across groups.
Modern subunit vaccines are composed of antigens and a delivery system and/or adjuvant (immune stimulator) that triggers the desired immune responses. Adjuvants mimic pathogen-associated molecular ...patterns (PAMPs) that are typically associated with infections. Carbohydrates displayed on the surface of pathogens are often recognized as PAMPs by receptors on antigen-presenting cells (APCs). Consequently, carbohydrates and their analogues have been used as adjuvants and delivery systems to promote antigen transport to APCs. Carbohydrates are biocompatible, usually nontoxic, biodegradable, and some are mucoadhesive. As such, carbohydrates and their derivatives have been intensively explored for the development of new adjuvants. This review assesses the immunological functions of carbohydrate ligands and their ability to enhance systemic and mucosal immune responses against co-administered antigens. The role of carbohydrate-based adjuvants/delivery systems in the development of subunit vaccines is discussed in detail.
Peptide-based subunit nanovaccines Skwarczynski, Mariusz; Toth, Istvan
Current drug delivery,
05/2011, Letnik:
8, Številka:
3
Journal Article
Recenzirano
Classical vaccines incorporating live or attenuated microorganisms possess several disadvantages and cannot be applied against cancer and some pathogens. Modern vaccines utilizing immunogenic ...subunits derived from a particular pathogen are able to overcome these obstacles but need a specific delivery system for their efficacy. Nanotechnology has opened a new window into these delivery methodologies. A nano-sized formulation of subunit vaccines has been proven to be very effective in inducing cellular and humoral immune responses. Here, we review a number of peptide vaccine delivery strategies based on nanoparticles composed of polymers, peptides, lipids, and inorganic materials.
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