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1.
Proc Natl Acad Sci U S A ; 119(14): e2119093119, 2022 04 05.
Article in English | MEDLINE | ID: covidwho-1751830

ABSTRACT

SignificanceUsing SARS-CoV-2 as a relevant case study for infectious disease, we investigate the structure-function relationships that dictate antiviral spherical nucleic acid (SNA) vaccine efficacy. We show that the SNA architecture can be rapidly employed to target COVID-19 through incorporation of the receptor-binding domain, and that the resulting vaccine potently activates human cells in vitro and mice in vivo. Furthermore, when challenged with a lethal viral infection, only mice treated with the SNA vaccine survived. Taken together, this work underscores the importance of rational vaccine design for infectious disease to yield vaccines that elicit more potent immune responses to effectively fight disease.


Subject(s)
Communicable Disease Control , Nucleic Acids/immunology , Vaccines, DNA/immunology , Animals , Biotechnology , COVID-19/prevention & control , Communicable Disease Control/methods , Communicable Diseases/etiology , Communicable Diseases/immunology , Humans , Nucleic Acids/chemistry , SARS-CoV-2/immunology , Vaccines, DNA/genetics , Viral Vaccines/genetics , Viral Vaccines/immunology
3.
Front Immunol ; 12: 838082, 2021.
Article in English | MEDLINE | ID: covidwho-1674340

ABSTRACT

Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future. Systematic Review Registration.


Subject(s)
Single-Domain Antibodies/chemistry , Single-Domain Antibodies/therapeutic use , Animals , Autoimmune Diseases/immunology , Autoimmune Diseases/therapy , Communicable Diseases/immunology , Communicable Diseases/therapy , Humans , Immunomodulation , Molecular Imaging , Molecular Targeted Therapy , Neoplasms/diagnostic imaging , Neoplasms/immunology , Neoplasms/therapy , Recombinant Proteins/chemistry , Recombinant Proteins/immunology , Recombinant Proteins/therapeutic use , Single-Domain Antibodies/immunology
4.
Emerg Microbes Infect ; 11(1): 384-391, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1615765

ABSTRACT

This paper presents the key outcomes of the above WHO informal consultation with global stakeholders including regulatory authorities, vaccine developers and manufacturers, academia and other international health organizations and institutions involved in the development, evaluation and use of messenger RNA (mRNA) vaccines. The aim of the consultation was to further clarify the main principles to be presented in an upcoming WHO guidance document on the regulatory considerations in evaluating the quality, safety and efficacy of mRNA prophylactic vaccines for infectious diseases. This WHO guidance document is intended to facilitate global mRNA vaccine development and regulatory convergence in the assessment of such vaccines. The urgent need to develop such a document as a new WHO written standard is outlined in this report along with the key scientific and regulatory challenges. A number of key conclusions are provided at the end of this report along with an update on the steps taken following this meeting.


Subject(s)
Communicable Disease Control/methods , Communicable Diseases/immunology , Vaccines, Synthetic/adverse effects , Vaccines, Synthetic/therapeutic use , /therapeutic use , COVID-19/prevention & control , Humans , Vaccine Potency , World Health Organization
5.
Curr Opin Immunol ; 72: 230-238, 2021 10.
Article in English | MEDLINE | ID: covidwho-1603901

ABSTRACT

The study of monogenic autoimmune diseases has provided key insights into molecular mechanisms involved in development of autoimmunity and immune tolerance. It has also become clear that such inborn errors of immunity (IEIs) frequently present clinically not only with autoimmune diseases, but also frequently have increased susceptibility to infection. The genes associated with monogenic autoimmunity influence diverse functional pathways, and the resulting immune dysregulation also impacts the complex and coordinated immune response to pathogens, for example type I interferon and cytokine signaling, the complement pathway and proper differentiation of the immune response. The SARS-CoV-2 pandemic has highlighted how monogenic autoimmunity can increase risk for serious infection with the discovery of severe disease in patients with pre-existing antibodies to Type I IFNs. This review discusses recent insight into the relationship between monogenic autoimmunity and infectious diseases.


Subject(s)
Autoimmune Diseases/immunology , COVID-19/immunology , Communicable Diseases/immunology , SARS-CoV-2/physiology , Animals , Autoimmune Diseases/genetics , COVID-19/genetics , Communicable Diseases/genetics , Disease Susceptibility , Humans , Interferon Type I/metabolism
7.
Acc Chem Res ; 54(23): 4283-4293, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1521679

ABSTRACT

After decades of extensive fundamental studies and clinical trials, lipid nanoparticles (LNPs) have demonstrated effective mRNA delivery such as the Moderna and Pfizer-BioNTech vaccines fighting against COVID-19. Moreover, researchers and clinicians have been investigating mRNA therapeutics for a variety of therapeutic indications including protein replacement therapy, genome editing, and cancer immunotherapy. To realize these therapeutics in the clinic, there are many formidable challenges. First, novel delivery systems such as LNPs with high delivery efficiency and low toxicity need to be developed for different cell types. Second, mRNA molecules need to be engineered for improved pharmaceutical properties. Lastly, the LNP-mRNA nanoparticle formulations need to match their therapeutic applications.In this Account, we summarize our recent advances in the design and development of various classes of lipids and lipid derivatives, which can be formulated with multiple types of mRNA molecules to treat diverse diseases. For example, we conceived a series of ionizable lipid-like molecules based on the structures of a benzene core, an amide linker, and hydrophobic tails. We identified N1,N3,N5-tris(3-(didodecylamino)propyl)benzene-1,3,5-tricarboxamide (TT3) as a lead compound for mRNA delivery both in vitro and in vivo. Moreover, we tuned the biodegradability of these lipid-like molecules by introducing branched ester or linear ester chains. Meanwhile, inspired by biomimetic compounds, we synthesized vitamin-derived lipids, chemotherapeutic conjugated lipids, phospholipids, and glycolipids. These scaffolds greatly broaden the chemical space of ionizable lipids for mRNA delivery. In another section, we highlight our efforts on the research direction of mRNA engineering. We previously optimized mRNA chemistry using chemically-modified nucleotides to increase the protein expression, such as pseudouridine (ψ), 5-methoxyuridine (5moU), and N1-methylpseudouridine (me1ψ). Also, we engineered the sequences of mRNA 5' untranslated regions (5'-UTRs) and 3' untranslated regions (3'-UTRs), which dramatically enhanced protein expression. With the progress of LNP development and mRNA engineering, we consolidate these technologies and apply them to treat diseases such as genetic disorders, infectious diseases, and cancers. For instance, TT3 and its analog-derived lipid-like nanoparticles can effectively deliver factor IX or VIII mRNA and recover the clotting activity in hemophilia mouse models. Engineered mRNAs encoding SARS-CoV-2 antigens serve well as vaccine candidates against COVID-19. Vitamin-derived lipid nanoparticles loaded with antimicrobial peptide-cathepsin B mRNA enable adoptive macrophage transfer to treat multidrug resistant bacterial sepsis. Biomimetic lipids such as phospholipids formulated with mRNAs encoding costimulatory receptors lead to enhanced cancer immunotherapy.Overall, lipid-mRNA nanoparticle formulations have considerably benefited public health in the COVID-19 pandemic. To expand their applications in clinical use, research work from many disciplines such as chemistry, engineering, materials, pharmaceutical sciences, and medicine need to be integrated. With these collaborative efforts, we believe that more and more lipid-mRNA nanoparticle formulations will enter the clinic in the near future and benefit human health.


Subject(s)
Drug Carriers/chemistry , Liposomes/chemistry , Nanoparticles/chemistry , RNA, Messenger/chemistry , Animals , Benzamides/chemistry , Biomimetic Materials/chemistry , Communicable Diseases/immunology , Communicable Diseases/therapy , Disease Models, Animal , Genetic Diseases, Inborn/immunology , Genetic Diseases, Inborn/therapy , Humans , Mice , Neoplasms/immunology , Neoplasms/therapy , Phospholipids/chemistry , RNA, Messenger/metabolism , RNA, Messenger/therapeutic use , Untranslated Regions , Vitamins/chemistry
9.
Molecules ; 26(17)2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1436074

ABSTRACT

Nutraceutical, a term derived from 'nutrition' and 'pharmaceutical', refers to any product isolated from herbs, nutrients, specific diets, processed foods, and beverages used not only for nutritional but also for medicinal purposes [...].


Subject(s)
Communicable Diseases/immunology , Dietary Supplements , Gastrointestinal Diseases/immunology , Inflammation/immunology , Neoplasms/immunology , Nutritional Status/immunology , Humans
11.
Adv Drug Deliv Rev ; 176: 113867, 2021 09.
Article in English | MEDLINE | ID: covidwho-1312868

ABSTRACT

Prophylactic vaccines have evolved from traditional whole-cell vaccines to safer subunit vaccines. However, subunit vaccines still face problems, such as poor immunogenicity and low efficiency, while traditional adjuvants are usually unable to meet specific response needs. Advanced delivery vectors are important to overcome these barriers; they have favorable safety and effectiveness, tunable properties, precise location, and immunomodulatory capabilities. Nevertheless, there has been no systematic summary of the delivery systems to cover a wide range of infectious pathogens. We herein summarized and compared the delivery systems for major or epidemic infectious diseases caused by bacteria, viruses, fungi, and parasites. We also included the newly licensed vaccines (e.g., COVID-19 vaccines) and those close to licensure. Furthermore, we highlighted advanced delivery systems with high efficiency, cross-protection, or long-term protection against epidemic pathogens, and we put forward prospects and thoughts on the development of future prophylactic vaccines.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19/prevention & control , Communicable Diseases/therapy , Drug Delivery Systems/methods , Pre-Exposure Prophylaxis/methods , Animals , COVID-19/epidemiology , COVID-19/immunology , COVID-19 Vaccines/immunology , Communicable Diseases/epidemiology , Communicable Diseases/immunology , Epidemics/prevention & control , Humans , Liposomes , Nanoparticles/administration & dosage
12.
Adv Drug Deliv Rev ; 178: 113848, 2021 11.
Article in English | MEDLINE | ID: covidwho-1283843

ABSTRACT

The emergence of SARS-CoV-2, and the ensuing global pandemic, has resulted in an unprecedented response to identify therapies that can limit uncontrolled inflammation observed in patients with moderate to severe COVID-19. The immune pathology behind COVID-19 is complex and involves the activation and interaction of multiple systems including, but not limited to, complement, inflammasomes, endothelial as well as innate and adaptive immune cells to bring about a convoluted profile of inflammation, coagulation and tissue damage. To date, therapeutic approaches have focussed on inhibition of coagulation, untargeted immune suppression and/or cytokine-directed blocking agents. Regardless of recently achieved improvements in individual patient outcomes and survival rates, improved and focussed approaches targeting individual systems involved is needed to further improve prognosis and wellbeing. This review summarizes the current understanding of molecular and cellular systems involved in the pathophysiology of COVID-19, and their contribution to pathogen clearance and damage to then discuss possible therapeutic options involving immunomodulatory drug delivery systems as well as summarising the complex interplay between them.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Drug Delivery Systems/methods , Immunologic Factors/administration & dosage , Inflammasomes/antagonists & inhibitors , Adjuvants, Immunologic/administration & dosage , Animals , Antiviral Agents/immunology , COVID-19/immunology , Communicable Diseases/drug therapy , Communicable Diseases/immunology , Complement Activation/drug effects , Complement Activation/immunology , Drug Delivery Systems/trends , Humans , Immunologic Factors/immunology , Inflammasomes/immunology
13.
Front Immunol ; 12: 662266, 2021.
Article in English | MEDLINE | ID: covidwho-1247862

ABSTRACT

IL-36 is a member of the interleukin 1 cytokine family, which is currently experiencing a renaissance due to the growing understanding of its context-dependent roles and advances in our understanding of the inflammatory response. The immunological role of IL-36 has revealed its profound and indispensable functional roles in psoriasis, as well as in several inflammatory diseases, including inflammatory bowel disease (IBD), systemic lupus erythematosus, rheumatoid arthritis (RA) and cancer. More recently, an increasing body of evidence suggests that IL-36 plays a crucial role in viral, bacterial and fungal infections. There is a growing interest as to whether IL-36 contributes to host protective immune responses against infection as well as the potential implications of IL-36 for the development of new therapeutic strategies. In this review, we summarize the recent progress in understanding cellular expression, regulatory mechanisms and biological roles of IL-36 in infectious diseases, which suggest more specific strategies to maneuver IL-36 as a diagnostic or therapeutic target, especially in COVID-19.


Subject(s)
COVID-19/immunology , Communicable Diseases/immunology , Infections/immunology , Inflammation/immunology , Interleukin-1/immunology , Psoriasis/immunology , SARS-CoV-2/physiology , Humans , Molecular Targeted Therapy
14.
Drug Deliv Transl Res ; 11(4): 1498-1508, 2021 08.
Article in English | MEDLINE | ID: covidwho-1237565

ABSTRACT

Transdermal drug delivery systems (TDDS) have many advantages and represent an excellent alternative to oral delivery and hypodermic injections. TDDS are more convenient and less invasive tools for disease and viral infection treatment, prevention, detection, and surveillance. The emerging development of microneedles for TDDS has facilitated improved skin barrier penetration for the delivery of macromolecules or hydrophilic drugs. Microneedle TDDS patches can be fabricated to deliver virus vaccines and potentially provide a viable alternative vaccine modality that offers improved immunogenicity, thermostability, simplicity, safety, and compliance as well as sharp-waste reduction, increased cost-effectiveness, and the capacity for self-administration, which could improve vaccine distribution. These advantages make TDDS-based vaccine delivery an especially well-suited option for treatment of widespread viral infectious diseases including pandemics. Because microneedle-based bioassays employ transdermal extraction of interstitial fluid or blood, they can be used as a minimally invasive approach for surveying disease markers and providing point-of-care (POC) diagnostics. For cutaneous viral infections, TDDS can provide localized treatment with high specificity and less systemic toxicity. In summary, TDDS, especially those that employ microneedles, possess special attributes that can be leveraged to reduce morbidity and mortality from viral infectious diseases. In this regard, they may have considerable positive impact as a modality for improving global health. In this article, we introduce the possible role and summarize the current literature regarding TDDS applications for fighting common cutaneous or systemic viral infectious diseases, including herpes simplex, varicella or herpes zoster, warts, influenza, measles, and COVID-19.


Subject(s)
Antiviral Agents/administration & dosage , COVID-19/drug therapy , Drug Delivery Systems/methods , Microinjections/methods , Administration, Cutaneous , Animals , Antiviral Agents/immunology , Antiviral Agents/metabolism , COVID-19/immunology , COVID-19/metabolism , Communicable Diseases/drug therapy , Communicable Diseases/immunology , Communicable Diseases/metabolism , Drug Delivery Systems/trends , Humans , Microinjections/trends
15.
JAMA Netw Open ; 4(4): e215493, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1178961

ABSTRACT

Importance: Claims that spinal manipulative therapy (SMT) can improve immune function have increased substantially during the COVID-19 pandemic and may have contributed to the rapid spread of both accurate and inaccurate information (referred to as an infodemic by the World Health Organization). Objective: To identify, appraise, and synthesize the scientific literature on the efficacy and effectiveness of SMT in preventing the development of infectious disease or improving disease-specific outcomes in patients with infectious disease and to examine the association between SMT and selected immunological, endocrine, and other physiological biomarkers. Evidence Review: A literature search of MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Index to Chiropractic Literature, the Cochrane Central Register of Controlled Trials, and Embase was conducted from inception to April 15, 2020. Randomized clinical trials and cohort studies were included. Eligible studies were critically appraised, and evidence with high and acceptable quality was synthesized using the Synthesis Without Meta-Analysis guideline. Findings: A total of 2593 records were retrieved; after exclusions, 50 full-text articles were screened, and 16 articles reporting the findings of 13 studies comprising 795 participants were critically appraised. The literature search found no clinical studies that investigated the efficacy or effectiveness of SMT in preventing the development of infectious disease or improving disease-specific outcomes among patients with infectious disease. Eight articles reporting the results of 6 high- and acceptable-quality RCTs comprising 529 participants investigated the effect of SMT on biomarkers. Spinal manipulative therapy was not associated with changes in lymphocyte levels or physiological markers among patients with low back pain or participants who were asymptomatic compared with sham manipulation, a lecture series, and venipuncture control groups. Spinal manipulative therapy was associated with short-term changes in selected immunological biomarkers among asymptomatic participants compared with sham manipulation, a lecture series, and venipuncture control groups. Conclusions and Relevance: In this systematic review of 13 studies, no clinical evidence was found to support or refute claims that SMT was efficacious or effective in changing immune system outcomes. Although there were limited preliminary data from basic scientific studies suggesting that SMT may be associated with short-term changes in immunological and endocrine biomarkers, the clinical relevance of these findings is unknown. Given the lack of evidence that SMT is associated with the prevention of infectious diseases or improvements in immune function, further studies should be completed before claims of efficacy or effectiveness are made.


Subject(s)
COVID-19/therapy , Communicable Diseases/therapy , Manipulation, Chiropractic/methods , Manipulation, Spinal/methods , Physical Therapy Modalities , Biomarkers/analysis , COVID-19/immunology , Communicable Diseases/immunology , Humans , Immune System/physiopathology , Immune System/virology , Randomized Controlled Trials as Topic , SARS-CoV-2 , Treatment Outcome
16.
Biomolecules ; 11(3)2021 03 15.
Article in English | MEDLINE | ID: covidwho-1167410

ABSTRACT

Galectin-9 (Gal-9) is a ß-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.


Subject(s)
Communicable Diseases/blood , Galectins/blood , Acute Disease , Amino Acid Sequence , COVID-19/blood , COVID-19/physiopathology , Chronic Disease , Communicable Diseases/immunology , Communicable Diseases/physiopathology , Dengue/blood , Dengue/physiopathology , Galectins/genetics , Galectins/metabolism , HIV Infections/blood , HIV Infections/physiopathology , Humans , Immunologic Factors/metabolism , Leptospirosis/blood , Leptospirosis/physiopathology , Malaria/blood , Malaria/physiopathology , Tuberculosis/blood , Tuberculosis/physiopathology
17.
Int J Mol Sci ; 22(5)2021 Mar 08.
Article in English | MEDLINE | ID: covidwho-1134168

ABSTRACT

The fruit fly, Drosophila melanogaster, has been used to understand fundamental principles of genetics and biology for over a century. Drosophila is now also considered an essential tool to study mechanisms underlying numerous human genetic diseases. In this review, we will discuss how flies can be used to deepen our knowledge of infectious disease mechanisms in vivo. Flies make effective and applicable models for studying host-pathogen interactions thanks to their highly conserved innate immune systems and cellular processes commonly hijacked by pathogens. Drosophila researchers also possess the most powerful, rapid, and versatile tools for genetic manipulation in multicellular organisms. This allows for robust experiments in which specific pathogenic proteins can be expressed either one at a time or in conjunction with each other to dissect the molecular functions of each virulent factor in a cell-type-specific manner. Well documented phenotypes allow large genetic and pharmacological screens to be performed with relative ease using huge collections of mutant and transgenic strains that are publicly available. These factors combine to make Drosophila a powerful tool for dissecting out host-pathogen interactions as well as a tool to better understand how we can treat infectious diseases that pose risks to public health, including COVID-19, caused by SARS-CoV-2.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/metabolism , Drosophila melanogaster/immunology , Drosophila melanogaster/metabolism , Animals , Communicable Diseases/microbiology , Communicable Diseases/virology , Drosophila melanogaster/microbiology , Drosophila melanogaster/virology , Host-Pathogen Interactions , Immunity, Innate , Signal Transduction , Virulence Factors/metabolism
18.
PLoS Pathog ; 17(1): e1009220, 2021 01.
Article in English | MEDLINE | ID: covidwho-1088772

ABSTRACT

The eponymous member of the interferon regulatory factor (IRF) family, IRF1, was originally identified as a nuclear factor that binds and activates the promoters of type I interferon genes. However, subsequent studies using genetic knockouts or RNAi-mediated depletion of IRF1 provide a much broader view, linking IRF1 to a wide range of functions in protection against invading pathogens. Conserved throughout vertebrate evolution, IRF1 has been shown in recent years to mediate constitutive as well as inducible host defenses against a variety of viruses. Fine-tuning of these ancient IRF1-mediated host defenses, and countering strategies by pathogens to disarm IRF1, play crucial roles in pathogenesis and determining the outcome of infection.


Subject(s)
Communicable Diseases/immunology , Communicable Diseases/therapy , Host-Pathogen Interactions/immunology , Immunity, Innate/immunology , Interferon Regulatory Factor-1/metabolism , Animals , Communicable Diseases/metabolism , Humans , Interferon Regulatory Factor-1/immunology
19.
Nutrients ; 13(1)2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1067765

ABSTRACT

Reduced magnesium (Mg) intake is a frequent cause of deficiency with age together with reduced absorption, renal wasting, and polypharmacotherapy. Chronic Mg deficiency may result in increased oxidative stress and low-grade inflammation, which may be linked to several age-related diseases, including higher predisposition to infectious diseases. Mg might play a role in the immune response being a cofactor for immunoglobulin synthesis and other processes strictly associated with the function of T and B cells. Mg is necessary for the biosynthesis, transport, and activation of vitamin D, another key factor in the pathogenesis of infectious diseases. The regulation of cytosolic free Mg in immune cells involves Mg transport systems, such as the melastatin-like transient receptor potential 7 channel, the solute carrier family, and the magnesium transporter 1 (MAGT1). The functional importance of Mg transport in immunity was unknown until the description of the primary immunodeficiency XMEN (X-linked immunodeficiency with Mg defect, Epstein-Barr virus infection, and neoplasia) due to a genetic deficiency of MAGT1 characterized by chronic Epstein-Barr virus infection. This and other research reporting associations of Mg deficit with viral and bacterial infections indicate a possible role of Mg deficit in the recent coronavirus disease 2019 (COVID-19) and its complications. In this review, we will discuss the importance of Mg for the immune system and for infectious diseases, including the recent pandemic of COVID-19.


Subject(s)
Aging/physiology , COVID-19/metabolism , Communicable Diseases/metabolism , Magnesium Deficiency/complications , Magnesium/metabolism , Aged , COVID-19/etiology , COVID-19/immunology , COVID-19/virology , Cation Transport Proteins/metabolism , Communicable Diseases/immunology , Communicable Diseases/microbiology , Communicable Diseases/virology , Epstein-Barr Virus Infections/metabolism , Female , Humans , Magnesium/immunology , Magnesium Deficiency/immunology , Magnesium Deficiency/metabolism , Male , SARS-CoV-2/immunology , X-Linked Combined Immunodeficiency Diseases/metabolism
20.
Nat Nanotechnol ; 16(1): 16-24, 2021 01.
Article in English | MEDLINE | ID: covidwho-1065871

ABSTRACT

Infectious diseases, including the coronavirus disease 2019 (COVID-19) pandemic that has brought the world to a standstill, are emerging at an unprecedented rate with a substantial impact on public health and global economies. For many life-threatening global infectious diseases, such as human immunodeficiency virus (HIV) infection, malaria and influenza, effective vaccinations are still lacking. There are numerous roadblocks to developing new vaccines, including a limited understanding of immune correlates of protection to these global infections. To induce a reproducible, strong immune response against difficult pathogens, sophisticated nanovaccine technologies are under investigation. In contrast to conventional vaccines, nanovaccines provide improved access to lymph nodes, optimal packing and presentation of antigens, and induction of a persistent immune response. This Review provides a perspective on the global trends in emerging nanoscale vaccines for infectious diseases and describes the biological, experimental and logistical problems associated with their development, and how immunoengineering can be leveraged to overcome these challenges.


Subject(s)
B-Lymphocytes/immunology , Communicable Diseases/immunology , Nanoparticles/administration & dosage , Vaccines/immunology , Animals , Antibodies, Neutralizing , Antibody-Dependent Enhancement , Antigen Presentation , Communicable Diseases/pathology , Humans , Lymph Nodes/immunology , Microbiota/immunology , Mutation , Vaccines/administration & dosage
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