Iron is a critical metal for several vital biological processes. Most of the body’s iron is bound to hemoglobin in erythrocytes. Iron from senescent red blood cells is recycled by macrophages in the spleen, liver and bone marrow. Dietary iron is taken up by the divalent metal transporter 1 (DMT1) in enterocytes and transported to portal blood via ferroportin (FPN), where it is bound to transferrin and taken up by hepatocytes, macrophages and bone marrow cells via transferrin receptor 1 (TfR1). While most of the physiologically active iron is bound hemoglobin, the major storage of most iron occurs in the liver in a ferritin-bound fashion. In response to an increased iron load, hepatocytes secrete the peptide hormone hepcidin, which binds to and induces internalization and degradation of the iron transporter FPN, thus controlling the amount of iron released from the cells into the blood. This review summarizes the key mechanisms and players involved in cellular and systemic iron regulation.
Virus-like particles (VLPs) have become key tools in biology, medicine and even engineering. After their initial use to resolve viral structures at the atomic level, VLPs were rapidly harnessed to develop antiviral vaccines followed by their use as display platforms to generate any kind of vaccine. Most recently, VLPs have been employed as nanomachines to deliver pharmaceutically active products to specific sites and into specific cells in the body. Here, we focus on the use of VLPs for the development of vaccines with broad fields of indications ranging from classical vaccines against viruses to therapeutic vaccines against chronic inflammation, pain, allergy and cancer. In this review, we take a walk through time, starting with the latest developments in experimental preclinical VLP-based vaccines and ending with marketed vaccines, which earn billions of dollars every year, paving the way for the next wave of prophylactic and therapeutic vaccines already visible on the horizon.
Virus-like particles (VLPs) derived from viral nucleocapsids are an important class of nanoparticles. The structure, uniformity, stability, and function of these VLPs have attracted scientists in utilizing them as a unique tool in various applications in biomedical fields. Their interaction with the innate immune system is of major importance for the adaptive immune response they induce. The innate immune cells and molecules recognize and interact with VLPs on the basis of two major characteristics: size and surface geometry. This review discusses the interaction of viral capsid-derived VLPs with the innate immune system.
The first successful use of nanoparticles (NPs) for vaccination was reported almost 40 years ago with a virus-like particle-based vaccine against Hepatitis B. Since then, the term NP has been expanded to accommodate a large number of novel nano-sized particles engineered from a range of materials. The great interest in NPs is likely not only a result of the two successful vaccines against hepatitis B and Human Papilloma Virus (HPV) that use this technology, but also due to the versatility of those small-sized particles, as indicated by the wide range of applications reported so far, ranging from medicinal and cosmetics to purely technical applications. In this review, we will focus on the use of NPs, especially virus-like particles (VLPs), in the field of vaccines and will discuss their employment as vaccines, antigen display platforms, adjuvants and drug delivery systems.
27 August 2019 in WIREs Nanomedicine and Nanobiotechnology
Active immunotherapy of cancer aims to treat the disease by inducing effective cellular and humoral immune responses. Virus‐like particle‐based vaccines have evolved dramatically over the last few decades, greatly reducing morbidity and mortality of several infectious diseases and expectedly preventing cervical cancer caused by human papilloma virus. In contrast to these broad successes of disease prevention, therapeutic cancer vaccines remain to demonstrate clinical benefit. Yet, several preclinical and clinical trials have revealed promising results and are paving the way for medical breakthroughs. This study reviews and discusses the recent preclinical development and clinical trials in this field.This article is categorized under:Biology‐Inspired Nanomaterials > Protein and Virus‐Based StructuresNanotechnology Approaches to Biology > Nanoscale Systems in Biology
Vaccines need to be rationally designed in order be delivered to the immune system for maximizing induction of dynamic immune responses. Virus‐like particles (VLPs) are ideal platforms for such 3D vaccines, as they allow the display of complex and native antigens in a highly repetitive form on their surface and can easily reach lymphoid organs in intact form for optimal activation of B and T cells. Adjusting size and zeta potential may allow investigators to further fine‐tune delivery to lymphoid organs. An additional way to alter vaccine transfer to lymph nodes and spleen may be the formulation with micron‐sized adjuvants that creates a local depot and results in a slow release of antigen and adjuvant. Ideally, the adjuvant in addition stimulates the innate immune system. The dynamics of the immune response may be further enhanced by inclusion of Toll‐like receptor ligands, which many VLPs naturally package. Hence, considering the 3Ds in vaccine development may allow for enhancement of their attributes to tackle complex diseases, not usually amenable to conventional vaccine strategies.