scholarly journals Vaccine containing immunologic adjuvants with a wide range of activity to provide protection against COVID-19

2021 ◽  
Author(s):  
Mulugeta Berhanu
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Vaccine Development ◽  
Narrow Range ◽  
Wide Spectrum ◽  
Aluminum Salts ◽  
Global Problem ◽  
Wide Range ◽  
Immunologic Adjuvants

This paper proposes a wide spectrum immunologic adjuvant for vaccine development against COVID-19 which is the current global problem. It has been reported that a wide range of immune cells are involved in the body's response to SARS CoV2 infection. Therefore, vaccine with a wide-spectrum immunologic adjuvant can be used to provide protection against COVID-19. Lack of adjuvants that can induce the required immune responses is a serious impediment to vaccine development against this devastating virus. The approved adjuvants such as aluminum salts and MF59 exhibit a narrow range of activity. In an attempt to solve this problem, it is crucial to develop new adjuvants which can trigger a wide range of immune cells.

scholarly journals Vaccine containing immunologic adjuvants with a wide range of activity to provide protection against COVID-19

2021 ◽  
Author(s):  
Mulugeta Berhanu
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Vaccine Development ◽  
Narrow Range ◽  
Wide Spectrum ◽  
Aluminum Salts ◽  
Global Problem ◽  
Wide Range ◽  
Immunologic Adjuvants

This paper proposes a wide spectrum immunologic adjuvant for vaccine development against  COVID-19 which is the current global problem. It has been reported that a wide range of immune cells are involved in the body’s response to SARS CoV2 infection. Therefore, vaccine with a wide-spectrum immunologic adjuvant can be used to provide protection against COVID-19. Lack of adjuvants that can induce the required immune responses is a serious impediment to vaccine development against this devastating virus. The approved adjuvants such as aluminum salts and MF59 exhibit a narrow range of activity. In an attempt to solve this problem, it is crucial to develop new adjuvants which can trigger a wide range of immune cells.

scholarly journals Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 534 ◽  
Author(s):  
Vijayan ◽  
Mohapatra ◽  
Uthaman ◽  
Park
Keyword(s):  
Immune Responses ◽  
Targeted Delivery ◽  
Vaccine Development ◽  
Polymeric Nanoparticles ◽  
Vital Role ◽  
Effective Control ◽  
Therapeutic Vaccines ◽  
Hiv Therapy ◽  
Recent Advances ◽  
Wide Range

The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable vaccine candidates need to be designed to elicit appropriate immune responses. Nanotechnology has been found to play a unique role in the design of vaccines, providing them with enhanced specificity and potency. Nano-scaled materials, such as virus-like particles, liposomes, polymeric nanoparticles (NPs), and protein NPs, have received considerable attention over the past decade as potential carriers for the delivery of vaccine antigens and adjuvants, due to their beneficial advantages, like improved antigen stability, targeted delivery, and long-time release, for which antigens/adjuvants are either encapsulated within, or decorated on, the NP surface. Flexibility in the design of nanomedicine allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development. Biomimetic NPs have emerged as innovative natural mimicking biosystems that can be used for a wide range of biomedical applications. In this review, we discuss the recent advances in biomimetic nanovaccines, and their use in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and anti-tumor immunity.

scholarly journals Protective Immunity Against Neospora Caninum Infection Induced by 14-3-3 Protein in Mice

2020 ◽  
Author(s):  
Shan Li ◽  
Nan Zhang ◽  
Shaoxiong Liu ◽  
Jianhua Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Neospora Caninum ◽  
Survival Rates ◽  
Parasite Burden ◽  
Mouse Serum ◽  
Intermediate Hosts ◽  
Caninum Infection ◽  
Wide Range ◽  
Ifn Γ

Abstract BackgroundNeospora caninum causes infections in a wide range of intermediate hosts and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood.MethodsHere, we evaluated immune responses and protective effects of Nc14-3-3 against 2×107 Nc-1 tachyzoites. Antibody (IgG, IgGl and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum; survival rates; survival time; and parasite burdens were detected.ResultsIn the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum two weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8+ T lymphocytes in the spleens of mice, indicating that a significant cellular immune response was induced. Mouse survival rates and survival times were significantly prolonged after immunization survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, and 8 days after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a lower parasite burden and milder pathological changes in the mice immunized with Nc14-3-3.ConclusionsOur data demonstrate the vaccination of mice with Nc14-3-3 elicits both cellular and humoural immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.

Beyond dsRNA: Toll-like receptor 3 signalling in RNA-induced immune responses

2014 ◽  
Vol 458 (2) ◽  
pp. 195-201 ◽  
Author(s):  
Megumi Tatematsu ◽  
Tsukasa Seya ◽  
Misako Matsumoto
Keyword(s):  
Immune Responses ◽  
Transmembrane Protein ◽  
Wide Spectrum ◽  
Physiological Role ◽  
Structural Features ◽  
Dendritic Cell Maturation ◽  
Type I ◽  
Toll Like Receptor ◽  
Wide Range ◽  
Infection And Inflammation

The innate immune system recognizes pathogen- and damage-associated molecular patterns using pattern-recognition receptors that activate a wide range of signalling cascades to maintain host homoeostasis against infection and inflammation. Endosomal TLR3 (Toll-like receptor 3), a type I transmembrane protein, senses RNAs derived from cells with viral infection or sterile tissue damage, leading to the induction of type I interferon and cytokine production, as well as dendritic cell maturation. It has been accepted that TLR3 recognizes perfect dsRNA, but little has been addressed experimentally with regard to the structural features of virus- or host-derived RNAs that activate TLR3. Recently, a TLR3 agonist was identified, which was a virus-derived ‘structured’ RNA with incomplete stem structures. Both dsRNA and structured RNA are similarly internalized through clathrin- and raftlin-dependent endocytosis and delivered to endosomal TLR3. The dsRNA uptake machinery, in addition to TLR3, is critical for extracellular viral RNA-induced immune responses. A wide spectrum of TLR3 ligand structures beyond dsRNA and their delivery systems provide new insights into the physiological role of TLR3 in virus- or host-derived RNA-induced immune responses. In the present paper, we focus on the system for extracellular recognition of RNA and its delivery to TLR3.

scholarly journals Molecular Characterization of the Native (Non-Linked) CD160–HVEM Protein Complex Revealed by Initial Crystallographic Analysis

Crystals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 820
Author(s):  
Simona Lenhartová ◽  
Marek Nemčovič ◽  
Radka Šebová ◽  
Mário Benko ◽  
Dirk M. Zajonc ◽  
...  
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Cell Activation ◽  
Killer Cell ◽  
Crystallographic Analysis ◽  
Single Chain ◽  
Cell Parameters ◽  
Starting Point ◽  
Wide Range

An increasing number of surface-exposed ligands and receptors acting on immune cells are being considered as a starting point in drug development applications. As they are dedicated to manipulating a wide range of immune responses, accurately predicting their molecular interactions will be necessary for the development of safe and effective therapeutics to enhance immune responses and vaccination. Here, we focused on the characterization of human CD160 and HVEM immune receptors, whose mutual engagement leads to bidirectional signaling (e.g., T cell inhibition, natural killer cell activation or mucosal immunity). In particular, our study reports on the molecule preparation, characterization and initial crystallographic analysis of the CD160–HVEM complex and both HVEM and CD160 in the absence of their binding partner. Despite the importance of the CD160–HVEM immune signaling and its therapeutic relevance, the structural and mechanistic basis underlying CD160–HVEM engagement has some controversial evidence. On one hand, there are studies reporting on the CD160 molecule in monomeric form that was produced by refolding from bacterial cells, or as a covalently linked single-chain complex with its ligand HVEM in insect cells. On the other hand, there are older reports providing evidence on the multimeric form of CD160 that acts directly on immune cells. In our study, the native non-linked CD160–HVEM complex was co-expressed in the baculovirus insect host, purified to homogeneity by anion-exchange chromatography to provide missing evidence of the trimeric form in solution. Its trimeric existence was also confirmed by the initial crystallographic analysis. The native CD160–HVEM complex crystallized in the orthorhombic space group with unit cell parameters that could accommodate one trimeric complex (3:3) in an asymmetric unit, thus providing ample space for the multimeric form. Crystals of the CD160–HVEM complex, CD160 trimer and HVEM monomer (reported in two space groups) diffracted to a minimum Bragg spacing of 2.8, 3.1 and 1.9/2.1 Å resolution, respectively. The obtained data will lead to elucidating the native structure of the complex.

scholarly journals ROLE OF CXCR3 CHEMOKINE RECEPTOR AND ITS LIGANDS IN CERTAIN DISEASES

2019 ◽  
Vol 21 (4) ◽  
pp. 617-632 ◽  
Author(s):  
N. A. Arsentieva ◽  
A. V. Semenov ◽  
D. A. Zhebrun ◽  
E. V. Vasilyeva ◽  
Areg A. Totolian
Keyword(s):  
Immune Responses ◽  
Chemokine Receptor ◽  
Wide Spectrum ◽  
Control Cell ◽  
Autoimmune Disorders ◽  
Cell Polarization ◽  
Main Function ◽  
Activated T Cells ◽  
Wide Range

Chemokines are a special family of cytokines whose main function is to control cell migration; they are key players in the innate and adaptive immune responses. Directed chemotaxis of specific leukocyte subpopulations is necessary not only to maintain homeostasis, but also in development of some immunopathological conditions such as cancer, inflammation, infection, allergies and autoimmune disorders. Chemokines are pleiotropic molecules that are involved in physiological and pathophysiological processes. For example, the CXCR3 chemokine receptor is expressed on various cells: activated T and B lymphocytes, natural killers, eosinophils and neutrophils, dendritic cells, fibroblasts, endothelial and epithelial cells. Hence, CXCR3 and its ligands have a wide range of functional activity. CXCR3 ligands are the IFNγ-induced chemokines: CXCL9, CXCL10, CXCL11, and platelet-derived chemokines: CXCL4, CXCL4L1. All the CXCR3 ligands share common angiostatic properties due to lack of the Glu-Leu-Arg (ELR) motif. IFNγ-induced ligands of the CXCR3 are proinflammatory chemokines, they mainly recruit activated T cells and exert an effect on T cell polarization. Due to wide spectrum of biological activity, the ligands of CXCR3 receptor are involved in pathogenesis of various disorders, such as inflammation, infection, cancer, allergies and autoimmune disorders. In this review, we discuss the role of CXCR3 ligands in immunopathogenesis of various diseases, including the results of our studies in chronic hepatitis C, rheumatoid arthritis and pulmonary tuberculosis. Moreover, we have also discussed the potential laboratory diagnostic applicability of the chemokines in various diseases. This review illustrates a universal role of IFNγ-induced chemokines as mediators of immune responses in various diseases. The studies of CXCR3 ligands, their isoforms and receptors, interactions between themselves and with their receptors can provide a significant contribution to our understanding of the chemokine network. Understanding the system of IFNγ-dependent chemokines may have clinical implications, both for diagnostic tasks, and for therapeutic purposes.

scholarly journals Macrophages and the maintenance of homeostasis

2020 ◽  
Author(s):  
David M. Mosser ◽  
Kajal Hamidzadeh ◽  
Ricardo Goncalves
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Macrophage Polarization ◽  
The Body ◽  
Sensory Stimuli ◽  
Cellular Processes ◽  
Wide Range ◽  
Tissue Responses ◽  
Different Response

Abstract There have been many chapters written about macrophage polarization. These chapters generally focus on the role of macrophages in orchestrating immune responses by highlighting the T-cell-derived cytokines that shape these polarizing responses. This bias toward immunity is understandable, given the importance of macrophages to host defense. However, macrophages are ubiquitous and are involved in many different cellular processes, and describing them as immune cells is undoubtedly an oversimplification. It disregards their important roles in development, tissue remodeling, wound healing, angiogenesis, and metabolism, to name just a few processes. In this chapter, we propose that macrophages function as transducers in the body. According to Wikipedia, “A transducer is a device that converts energy from one form to another.” The word transducer is a term used to describe both the “sensor,” which can interpret a wide range of energy forms, and the “actuator,” which can switch voltages or currents to affect the environment. Macrophages are able to sense a seemingly endless variety of inputs from their environment and transduce these inputs into a variety of different response outcomes. Thus, rather than functioning as immune cells, they should be considered more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses. In this chapter, we will describe some of the sensory stimuli that macrophages perceive and the responses they make to these stimuli to achieve their prime directive, which is the maintenance of homeostasis.

scholarly journals Ghrelin as an Anti-Sepsis Peptide: Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Nimisha Mathur ◽  
Syed F. Mehdi ◽  
Manasa Anipindi ◽  
Monowar Aziz ◽  
Sawleha A. Khan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Immune Response ◽  
Immune Responses ◽  
Immune Cells ◽  
Inflammatory Agent ◽  
Wide Range ◽  
Inflammatory Processes ◽  
Anti Inflammatory ◽  
Preclinical Animal Models ◽  
Stimulation Of

Sepsis continues to produce widespread inflammation, illness, and death, prompting intensive research aimed at uncovering causes and therapies. In this article, we focus on ghrelin, an endogenous peptide with promise as a potent anti-inflammatory agent. Ghrelin was discovered, tracked, and isolated from stomach cells based on its ability to stimulate release of growth hormone. It also stimulates appetite and is shown to be anti-inflammatory in a wide range of tissues. The anti-inflammatory effects mediated by ghrelin are a result of both the stimulation of anti-inflammatory processes and an inhibition of pro-inflammatory forces. Anti-inflammatory processes are promoted in a broad range of tissues including the hypothalamus and vagus nerve as well as in a broad range of immune cells. Aged rodents have reduced levels of growth hormone (GH) and diminished immune responses; ghrelin administration boosts GH levels and immune response. The anti-inflammatory functions of ghrelin, well displayed in preclinical animal models of sepsis, are just being charted in patients, with expectations that ghrelin and growth hormone might improve outcomes in patients with sepsis.

scholarly journals Vaccines based on the cell surface carbohydrates of pathogenic bacteria

2005 ◽  
Vol 77 (2) ◽  
pp. 293-324 ◽  
Author(s):  
Christopher Jones
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Pathogenic Bacteria ◽  
Vaccine Development ◽  
Effective Means ◽  
Haemophilus Influenzae Type ◽  
Cell Surface Carbohydrate ◽  
Wide Range ◽  
Glycoconjugate Vaccines ◽  
Surface Carbohydrates

Glycoconjugate vaccines, in which a cell surface carbohydrate from a micro-organism is covalently attached to an appropriate carrier protein are proving to be the most effective means to generate protective immune responses to prevent a wide range of diseases. The technology appears to be generic and applicable to a wide range of pathogens, as long as antibodies against surface carbohydrates help protect against infection. Three such vaccines, against Haemophilus influenzae type b, Neisseria meningitidis Group C and seven serotypes of Streptococcus pneumoniae, have already been licensed and many others are in development. This article discusses the rationale for the development and use of glycoconjugate vaccines, the mechanisms by which they elicit T cell-dependent immune responses and the implications of this for vaccine development, the role of physicochemical methods in the characterisation and quality control of these vaccines, and the novel products which are under development.

Cucurbitacins as Anticancer Agents: A Patent Review

2019 ◽  
Vol 14 (2) ◽  
pp. 133-143 ◽  
Author(s):  
Hidayat Hussain ◽  
Ivan R. Green ◽  
Muhammad Saleem ◽  
Khanzadi F. Khattak ◽  
Muhammad Irshad ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Wide Spectrum ◽  
Biological Effects ◽  
Therapeutic Effects ◽  
Cytotoxic Effects ◽  
Natural Sources ◽  
Oh Groups ◽  
Drug Candidates ◽  
The Past ◽  
Wide Range

Background: Cucurbitacins belong to a group of tetracyclic triterpenoids that display a wide range of biological effects. In the past, numerous cucurbitacins have been isolated from natural sources and many active compounds have been synthesized using the privileged scaffold in order to enhance its cytotoxic effects. Objective: his review covers patents on the therapeutic effects of natural cucurbitacins and their synthetic analogs published during the past decade. By far, the majority of patents published are related to cancer and Structure-Activity Relationships (SAR) of these compounds are included to lend gravitas to this important class of natural products. Methods: The date about the published patents was downloaded via online open access patent databases. Results: Cucurbitacins display significant cytotoxic properties, in particular cucurbitacins B and D which possess very potent effects towards a number of cancer cells. Numerous cucurbitacins isolated from natural sources have been derivatized through chemical modification at the C(2)-OH and C(25)- OH groups. Most importantly, an acyl ester of the C(25)-OH and, iso-propyl, n-propyl and ethyl ether groups of the C(2)-OH demonstrated the most increased cytotoxic activity. Conclusion: The significant cytotoxic effects of natural and semi-synthetic cucurbitacins make them attractive as new drug candidates. Moreover, cucurbitacins have the capability to form conjugates with other anticancer drugs which will synergistically enhance their anticancer effects. The authors believe that in order to get lead compounds, there should be a greater focus on the synthesis of homodimers, heterodimers, and halo derivatives of cucurbitacins. In the opinion of the authors the analysis of the published patents on the cucurbitacins indicates that these compounds can be developed into a regimen to treat a wide spectrum of cancers.

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