scholarly journals Agonists of Receptors of the Innate Immunity and Defective Viral Particles as New Generation of Adjuvants

2018 ◽  
Vol 17 (1) ◽  
pp. 76-86
Author(s):  
O. A. Svitich ◽  
V. F. Lavrov ◽  
P. I. Kukina ◽  
A. A. Iskandaryan ◽  
L. V. Gankovskaya ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Poly I:C ◽  
Vaccine Adjuvants ◽  
Toll Like Receptor ◽  
Traditional Methods ◽  
Viral Particles ◽  
Pathogen Recognition Receptors ◽  
Molecular Patterns ◽  
New Generation

Vaccines for many years act as one of the most effective and successfully used medicines. Vaccines obtained by traditional methods contain in their composition live, weakened or killed microorganisms (bacteria, viruses, etc.). Now more often, modern, split, subunit, recombinant, polyvalent and some other types of vaccines are being used. The addition of adjuvants to vaccines generally increases the immune response to their administration. It was established that the formation of postvaccinal immunity begins immediately after the introduction of the vaccine, by activating the factors of innate immunity in the interaction of pathogen-associated molecular patterns (PAMPs), in vaccines, with the pathogen-recognition receptors (PRRs) of the immunocompetent cells of the recipient. It is also shown that PRRs activators, including TOLL-like receptor agonists (TLRs) and poly (I:C) polynucleotide oligomers of inosine and cytidylic acids, have the ability to substantially increase the immunogenicity of vaccines, and attempts are being made to use them creation of new types of adjuvants. Defective interfering viral particles (D-particles, DIPs) are also classed as effective stimulants of innate immunity and can also be considered promising vaccine adjuvants. 

scholarly journals Peptide Aggregation Induced Immunogenic Rupture (PAIIR)

2021 ◽  
Author(s):  
Gokhan Gunay ◽  
Seren Hamsici ◽  
Handan Acar ◽  
Mark L. Lang ◽  
Gillian A. Lang ◽  
...  
Keyword(s):  
Immune Response ◽  
Membrane Damage ◽  
Cell Types ◽  
Peptide Aggregation ◽  
Vaccine Adjuvants ◽  
Humoral And Cellular Immunity ◽  
Influenza Hemagglutinin ◽  
Series Of Experiments ◽  
Molecular Patterns

Under the influence of stress and membrane damage, cells undergo immunogenic cell death (ICD), which involves the release of damage associated molecular patterns (DAMPs), natural adjuvants for enhancing an immune response. In the presence of an antigen, released DAMPs can determine the type and magnitude of the immune response, and therefore the longevity and efficacy of an antigen-specific immunity. In the last decade, the immune response effect of ICD has been shown, yet there is no tool that can induce controlled ICD with predictable results, regardless of the cell type. We designed a peptide-based tool, called [II], for controlled damage to cell membrane to induce ICD and DAMPs release. Herein we describe a series of experiments that determine that the mechanism of action of [II] includes a caspase-dependent ICD and subsequent release of immune stimulating DAMPs, on various cell types. Moreover, we tested the hypothesis that controlled DAMP release via [II] in vivo was associated with enhancement of antigen-specific adaptive immunity with influenza hemagglutinin (HA) subunit vaccine. HA and [II] showed significantly higher HA specific IgG1 and IgG2a antibodies, compared to HA-only immunized mice, while the peptide itself did not elicit antibodies. In this paper, we demonstrate the first peptide-aggregation induced immunogenic rupture (PAIIR) approach as vaccine adjuvants for increasing both humoral and cellular immunity. In consideration of its ability to enhance IgG2a responses that are associated with heterosubtypic influenza virus protection, PAIIR is a promising adjuvant to promote universal protection upon influenza HA vaccination.

scholarly journals Innate Immune Response against Hepatitis C Virus: Targets for Vaccine Adjuvants

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 313
Author(s):  
Daniel Sepulveda-Crespo ◽  
Salvador Resino ◽  
Isidoro Martinez
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Innate Immune Response ◽  
Vaccine Development ◽  
Innate Immune ◽  
World Health ◽  
Cell Immune Response ◽  
Vaccine Adjuvants

Despite successful treatments, hepatitis C virus (HCV) infections continue to be a significant world health problem. High treatment costs, the high number of undiagnosed individuals, and the difficulty to access to treatment, particularly in marginalized susceptible populations, make it improbable to achieve the global control of the virus in the absence of an effective preventive vaccine. Current vaccine development is mostly focused on weakly immunogenic subunits, such as surface glycoproteins or non-structural proteins, in the case of HCV. Adjuvants are critical components of vaccine formulations that increase immunogenic performance. As we learn more information about how adjuvants work, it is becoming clear that proper stimulation of innate immunity is crucial to achieving a successful immunization. Several hepatic cell types participate in the early innate immune response and the subsequent inflammation and activation of the adaptive response, principally hepatocytes, and antigen-presenting cells (Kupffer cells, and dendritic cells). Innate pattern recognition receptors on these cells, mainly toll-like receptors, are targets for new promising adjuvants. Moreover, complex adjuvants that stimulate different components of the innate immunity are showing encouraging results and are being incorporated in current vaccines. Recent studies on HCV-vaccine adjuvants have shown that the induction of a strong T- and B-cell immune response might be enhanced by choosing the right adjuvant.

Synthetic molecules and functionalized nanoparticles targeting the LPS-TLR4 signaling: A new generation of immunotherapeutics

2011 ◽  
Vol 84 (1) ◽  
pp. 97-106 ◽  
Author(s):  
Francesco Peri ◽  
Valentina Calabrese ◽  
Matteo Piazza ◽  
Roberto Cighetti
Keyword(s):  
Myeloid Differentiation ◽  
Vaccine Adjuvants ◽  
Toll Like Receptor ◽  
Differentiation Antigen ◽  
Toll Like Receptor 4 ◽  
Tlr4 Signaling ◽  
Bacterial Endotoxins ◽  
Pharmacological Interest ◽  
Tlr4 Activation ◽  
New Generation

Toll-like receptor 4 (TLR4), the receptor of bacterial endotoxins in mammalians, plays a pivotal role in the induction of innate immunity and inflammation. TLR4 activation by bacterial lipopolysaccharide (LPS) is achieved by the coordinate and sequential action of three other proteins, the lipopolysaccharide binding protein (LBP), the cluster differentiation antigen CD14, and the myeloid differentiation protein (MD-2) receptors, that bind LPS and present it in a monomeric form to TLR4 by forming the activated [TLR4·MD-2·LPS]2 complex. Small molecules and nanoparticles active in modulating the TLR4 signal by targeting directly the MD-2·TLR4 complex or by interfering in other points of the TLR4 signaling are presented in this paper. These compounds have great pharmacological interest as vaccine adjuvants, immunotherapeutics, anti-sepsis, and anti-inflammatory agents.

scholarly journals Exploration of Pattern Recognition Receptor Agonists as Candidate Adjuvants

2021 ◽  
Vol 11 ◽  
Author(s):  
Guang Han Ong ◽  
Benedict Shi Xiang Lian ◽  
Takumi Kawasaki ◽  
Taro Kawai
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Host Cells ◽  
Vaccine Adjuvants ◽  
Immune Reactions ◽  
Safety And Reliability ◽  
Pathogen Recognition Receptors ◽  
Acquired Immune Responses ◽  
Molecular Patterns

Adjuvants are used to maximize the potency of vaccines by enhancing immune reactions. Components of adjuvants include pathogen-associated molecular patterns (PAMPs) and damage-associate molecular patterns (DAMPs) that are agonists for innate immune receptors. Innate immune responses are usually activated when pathogen recognition receptors (PRRs) recognize PAMPs derived from invading pathogens or DAMPs released by host cells upon tissue damage. Activation of innate immunity by PRR agonists in adjuvants activates acquired immune responses, which is crucial to enhance immune reactions against the targeted pathogen. For example, agonists for Toll-like receptors have yielded promising results as adjuvants, which target PRR as adjuvant candidates. However, a comprehensive understanding of the type of immunological reaction against agonists for PRRs is essential to ensure the safety and reliability of vaccine adjuvants. This review provides an overview of the current progress in development of PRR agonists as vaccine adjuvants, the molecular mechanisms that underlie activation of immune responses, and the enhancement of vaccine efficacy by these potential adjuvant candidates.

scholarly journals Neutrophil Extracellular Traps (NETs) and Damage-Associated Molecular Patterns (DAMPs): Two Potential Targets for COVID-19 Treatment

2020 ◽  
Vol 2020 ◽  
pp. 1-25 ◽  
Author(s):  
Sebastiano Cicco ◽  
Gerolamo Cicco ◽  
Vito Racanelli ◽  
Angelo Vacca
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Targeted Therapy ◽  
High Mobility ◽  
Neutrophil Extracellular Traps ◽  
Lung Cells ◽  
Extracellular Traps ◽  
Molecular Patterns ◽  
Damage Associated Molecular Patterns ◽  
Excessive Inflammatory Response

COVID-19 is a pandemic disease caused by the new coronavirus SARS-CoV-2 that mostly affects the respiratory system. The consequent inflammation is not able to clear viruses. The persistent excessive inflammatory response can build up a clinical picture that is very difficult to manage and potentially fatal. Modulating the immune response plays a key role in fighting the disease. One of the main defence systems is the activation of neutrophils that release neutrophil extracellular traps (NETs) under the stimulus of autophagy. Various molecules can induce NETosis and autophagy; some potent activators are damage-associated molecular patterns (DAMPs) and, in particular, the high-mobility group box 1 (HMGB1). This molecule is released by damaged lung cells and can induce a robust innate immunity response. The increase in HMGB1 and NETosis could lead to sustained inflammation due to SARS-CoV-2 infection. Therefore, blocking these molecules might be useful in COVID-19 treatment and should be further studied in the context of targeted therapy.

scholarly journals The Immune Response toTrypanosoma cruzi: Role of Toll-Like Receptors and Perspectives for Vaccine Development

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Mauricio M. Rodrigues ◽  
Ana Carolina Oliveira ◽  
Maria Bellio
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccine Development ◽  
State Of The Art ◽  
Toll Like Receptor ◽  
Vaccine Research ◽  
The Past ◽  
Acquired Immune Responses ◽  
Molecular Patterns

In the past ten years, studies have shown the recognition ofTrypanosoma cruzi-associated molecular patterns by members of the Toll-like receptor (TLR) family and demonstrated the crucial participation of different TLRs during the experimental infection with this parasite. In the present review, we will focus on the role of TLR-activated pathways in the modulation of both innate and acquired immune responses toT. cruziinfection, as well as discuss the state of the art of vaccine research and development against the causative agent of Chagas disease (or American trypanosomiasis).

scholarly journals The Role of Bacteria and Pattern Recognition Receptors in GvHD

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
E. Holler ◽  
K. Landfried ◽  
J. Meier ◽  
M. Hausmann ◽  
G. Rogler
Keyword(s):  
Innate Immunity ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Long Time ◽  
Potential Risk Factors ◽  
Pathogen Recognition Receptors ◽  
Antigen Presenting ◽  
Molecular Patterns ◽  
Gastrointestinal Decontamination

Graft-versus-Host Disease (GvHD) is the most serious complication of allogeneic stem cell transplantation (SCT) and results from an activation of donor lymphocytes by recipient antigen-presenting cells (APCs). For a long time, it has been postulated that the intestinal microflora and endotoxin exert a crucial step in this APC activation, as there is early and severe gastrointestinal damage induced by pretransplant conditioning. With the detailed description of pathogen-associated molecular patterns and pathogen recognition receptors single nucleotide polymorphisms of TLRs and especially NOD2 have been identified as potential risk factors of GvHD and transplant related complications thus further supporting the crucial role of innate immunity in SCT, related complications. Gastrointestinal decontamination and neutralization of endotoxin have been used to interfere with this early axis of activation with some success but more specific approaches of modulation of innate immunity are needed for further improvement of clinical outcome.

scholarly journals Danger Signals Activating the Immune Response after Trauma

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Stefanie Hirsiger ◽  
Hans-Peter Simmen ◽  
Clément M. L. Werner ◽  
Guido A. Wanner ◽  
Daniel Rittirsch
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Interleukin 1 ◽  
High Mobility ◽  
Dual Function ◽  
Interleukin 33 ◽  
Danger Theory ◽  
Danger Signals ◽  
Pathogen Recognition Receptors ◽  
Molecular Patterns

Sterile injury can cause a systemic inflammatory response syndrome (SIRS) that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins) as well as exogenous pathogen-associated molecular patterns (PAMPs) play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1), interleukin-1α(IL-1α), and interleukin-33 (IL-33) as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

scholarly journals The Yin and Yang of Innate Immunity in Stroke

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaomeng Xu ◽  
Yongjun Jiang
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Ischemic Stroke ◽  
Immune System ◽  
Innate Immune Response ◽  
Time Window ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Yin And Yang ◽  
Molecular Patterns

Immune system plays an elementary role in the pathophysiological progress of ischemic stroke. It consists of innate and adaptive immune system. Activated within minutes after ischemic onset, innate immunity is responsible for the elimination of necrotic cells and tissue repair, while it is critically involved in the initiation and amplification of poststroke inflammation that amplifies ischemic damage to the brain tissue. Innate immune response requires days to be fully developed, providing a considerable time window for therapeutic intervention, suggesting prospect of novel immunomodulatory therapies against poststroke inflammation-induced brain injury. However, obstacles still exist and a comprehensive understanding of ischemic stroke and innate immune reaction is essential. In this review, we highlighted the current experimental and clinical data depicting the innate immune response following ischemic stroke, mainly focusing on the recognition of damage-associated molecular patterns, activation and recruitment of innate immune cells, and involvement of various cytokines. In addition, clinical trials targeting innate immunity were also documented regardless of the outcome, stressing the requirements for further investigation.

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