scholarly journals Distinct single-component adjuvants steer human DC-mediated T-cell polarization via Toll-like receptor signaling toward a potent antiviral immune response

2021 ◽  
Vol 118 (39) ◽  
pp. e2103651118
Author(s):  
Laura Roßmann ◽  
Katrin Bagola ◽  
Tharshana Stephen ◽  
Anna-Lisa Gerards ◽  
Bianca Walber ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Vaccine Development ◽  
Nk Cell ◽  
Checkpoint Inhibitors ◽  
Cell Polarization ◽  
Vaccine Adjuvants ◽  
Toll Like Receptor ◽  
Antiviral Immune Response ◽  
Monophosphoryl Lipid A

The COVID-19 pandemic highlights the importance of efficient and safe vaccine development. Vaccine adjuvants are essential to boost and tailor the immune response to the corresponding pathogen. To allow for an educated selection, we assessed the effect of different adjuvants on human monocyte-derived dendritic cells (DCs) and their ability to polarize innate and adaptive immune responses. In contrast to commonly used adjuvants, such as aluminum hydroxide, Toll-like receptor (TLR) agonists induced robust phenotypic and functional DC maturation. In a DC-lymphocyte coculture system, we investigated the ensuing immune reactions. While monophosphoryl lipid A synthetic, a TLR4 ligand, induced checkpoint inhibitors indicative for immune exhaustion, the TLR7/8 agonist Resiquimod (R848) induced prominent type-1 interferon and interleukin 6 responses and robust CTL, B-cell, and NK-cell proliferation, which is particularly suited for antiviral immune responses. The recently licensed COVID-19 vaccines, BNT162b and mRNA-1273, are both based on single-stranded RNA. Indeed, we could confirm that the cytokine profile induced by lipid-complexed RNA was almost identical to the pattern induced by R848. Although this awaits further investigation, our results suggest that their efficacy involves the highly efficient antiviral response pattern stimulated by the RNAs’ TLR7/8 activation.

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 Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

scholarly journals The Sp1-Responsive microRNA-15b Negatively Regulates Rhabdovirus-Triggered Innate Immune Responses in Lower Vertebrates by Targeting TBK1

2021 ◽  
Vol 11 ◽  
Author(s):  
Renjie Chang ◽  
Qing Chu ◽  
Weiwei Zheng ◽  
Lei Zhang ◽  
Tianjun Xu
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune ◽  
Infection Model ◽  
Regulation Mechanism ◽  
Type I ◽  
Innate Immune Responses ◽  
Positive Role ◽  
Siniperca Chuatsi ◽  
Antiviral Immune Response

As is known to all, the production of type I interferon (IFN) plays pivotal roles in host innate antiviral immunity, and its moderate production play a positive role in promoting the activation of host innate antiviral immune response. However, the virus will establish a persistent infection model by interfering with the production of IFN, thereby evading the organism inherent antiviral immune response. Therefore, it is of great necessity to research the underlying regulatory mechanisms of type I IFN appropriate production under viral invasion. In this study, we report that a Sp1–responsive miR-15b plays a negative role in siniperca chuatsi rhabdovirus (SCRV)-triggered antiviral response in teleost fish. We found that SCRV could dramatically upregulate miiuy croaker miR-15b expression. Enhanced miR-15b could negatively regulate SCRV-triggered antiviral genes and inflammatory cytokines production by targeting TANK-binding kinase 1 (TBK1), thereby accelerating viral replication. Importantly, we found that miR-15b feedback regulates antiviral innate immune response through NF-κB and IRF3 signaling pathways. These findings highlight that miR-15b plays a crucial role in regulating virus–host interactions, which outlines a new regulation mechanism of fish’s innate immune responses.

Rhamnose modified bovine serum albumin as a carrier protein promotes the immune response against sTn antigen

2020 ◽  
Vol 56 (90) ◽  
pp. 13959-13962
Author(s):  
Han Lin ◽  
Haofei Hong ◽  
Jinfeng Wang ◽  
Chen Li ◽  
Zhifang Zhou ◽  
...  
Keyword(s):  
Immune Response ◽  
Bovine Serum Albumin ◽  
Immune Responses ◽  
Serum Albumin ◽  
Cancer Vaccine ◽  
Bovine Serum ◽  
Vaccine Development ◽  
Carrier Protein ◽  
Antigen Uptake ◽  
Specific Antibodies

Rhamnose and sTn antigen were co-conjugated to bovine serum albumin (BSA) for cancer vaccine development. The immune responses against sTn have been significantly augmented with the involvement of Rha-specific antibodies to enhance antigen uptake.

scholarly journals Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Xiuran Wang ◽  
Amit K. Singh ◽  
Xiangmin Zhang ◽  
Wei Sun
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Rational Design ◽  
Lipid A ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Outer Membrane Vesicles ◽  
Vector System ◽  
Content Type ◽  
Monophosphoryl Lipid A

ABSTRACT A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in mice against subcutaneous challenge with 8 × 105 CFU (80,000 50% lethal dose [LD50]) and intranasal challenge with 5 × 103 CFU (50 LD50) of virulent Y. pestis. This protection was significantly superior to that resulting from vaccination with LcrV/alhydrogel or rF1-V/alhydrogel. At week 4 postimmunization, the OMV-immunized mice showed more robust titers of antibodies against LcrV, Y. pestis whole-cell lysate (YPL), and F1 antigen and more balanced IgG1:IgG2a/IgG2b-derived Th1 and Th2 responses than LcrV-immunized mice. Moreover, potent adaptive and innate immune responses were stimulated in the OMV-immunized mice. Our findings demonstrate that self-adjuvanting Y. pestis OMVs provide a novel plague vaccine candidate and that the rational design of OMVs could serve as a robust approach for vaccine development.

scholarly journals Dual Role of Toll-Like Receptor 7 in the Pathogenesis of Rabies Virus in a Mouse Model

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Zhaochen Luo ◽  
Lei Lv ◽  
Yingying Li ◽  
Baokun Sui ◽  
Qiong Wu ◽  
...  
Keyword(s):  
Immune Response ◽  
Mouse Model ◽  
Immune Responses ◽  
Rabies Virus ◽  
Mouse Brain ◽  
Early Stage ◽  
Toll Like Receptor ◽  
Innate Recognition ◽  
Recognition Receptor

ABSTRACT Rabies, caused by rabies virus (RABV), is a fatal encephalitis in humans and other mammals, which continues to present a public health threat in most parts of the world. Our previous study demonstrated that Toll-like receptor 7 (TLR7) is essential in the induction of anti-RABV antibodies via the facilitation of germinal center formation. In the present study, we investigated the role of TLR7 in the pathogenicity of RABV in a mouse model. Using isolated plasmacytoid dendritic cells (pDCs), we demonstrated that TLR7 is an innate recognition receptor for RABV. When RABV invaded from the periphery, TLR7 detected viral single-stranded RNA and triggered immune responses that limited the virus’s entry into the central nervous system (CNS). When RABV had invaded the CNS, its detection by TLR7 led to the production of cytokines and chemokines and an increase the permeability of the blood-brain barrier. Consequently, peripheral immune cells, including pDCs, macrophages, neutrophils, and B cells infiltrated the CNS. While this immune response, triggered by TLR7, helped to clear viruses, it also increased neuroinflammation and caused immunopathology in the mouse brain. Our results demonstrate that TLR7 is an innate recognition receptor for RABV, which restricts RABV invasion into the CNS in the early stage of viral infection but also contributes to immunopathology by inducing neuroinflammation. IMPORTANCE Developing targeted treatment for RABV requires understanding the innate immune response to the virus because early virus clearance is essential for preventing the fatality when the infection has progressed to the CNS. Previous studies have revealed that TLR7 is involved in the immune response to RABV. Here, we establish that TLR7 recognizes RABV and facilitates the production of some interferon-stimulated genes. We also demonstrated that when RABV invades into the CNS, TLR7 enhances the production of inflammatory cytokines which contribute to immunopathology in the mouse brain. Taken together, our findings suggest that treatments for RABV must consider the balance between the beneficial and harmful effects of TLR7-triggered immune responses.

scholarly journals Chemical and Immunological Characteristics of Aluminum-Based, Oil-Water Emulsion, and Bacterial-Origin Adjuvants

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Susana Martiñón ◽  
Angel Cisneros ◽  
Sergio Villicaña ◽  
Ricardo Hernández-Miramontes ◽  
Edgar Mixcoha ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Lipid A ◽  
Humoral Response ◽  
Main Concern ◽  
Protein Antigens ◽  
Water Emulsion ◽  
Bacterial Origin ◽  
Monophosphoryl Lipid A ◽  
Oil Water

Adjuvants are a diverse family of substances whose main objective is to increase the strength, quality, and duration of the immune response caused by vaccines. The most commonly used adjuvants are aluminum-based, oil-water emulsion, and bacterial-origin adjuvants. In this paper, we will discuss how the election of adjuvants is important for the adjuvant-mediated induction of immunity for different types of vaccines. Aluminum-based adjuvants are the most commonly used, the safest, and have the best efficacy, due to the triggering of a strong humoral response, albeit generating a weak induction of cell-mediated immune response. Freund’s adjuvant is the most widely used oil-water emulsion adjuvant in animal trials; it stimulates inflammation and causes aggregation and precipitation of soluble protein antigens that facilitate the uptake by antigen-presenting cells (APCs). Adjuvants of bacterial origin, such as flagellin,E. colimembranes, and monophosphoryl lipid A (MLA), are known to potentiate immune responses, but their safety and risks are the main concern of their clinical use. This minireview summarizes the mechanisms that classic and novel adjuvants produce to stimulate immune responses.

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.

scholarly journals Impact of Toll-Like Receptor-Specific Agonists on the Host Immune Response to the Yersinia pestis Plague rF1V Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Sergei Biryukov ◽  
Jennifer L. Dankmeyer ◽  
Zain Shamsuddin ◽  
Ivan Velez ◽  
Nathaniel O. Rill ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Fusion Protein ◽  
Yersinia Pestis ◽  
Vaccine Efficacy ◽  
Host Immune Response ◽  
Toll Like Receptor ◽  
Vaccine Strategy ◽  
Pneumonic Plague ◽  
Plague Vaccine

Relatively recent advances in plague vaccinology have produced the recombinant fusion protein F1-V plague vaccine. This vaccine has been shown to readily protect mice from both bubonic and pneumonic plague. The protection afforded by this vaccine is solely based upon the immune response elicited by the F1 or V epitopes expressed on the F1-V fusion protein. Accordingly, questions remain surrounding its efficacy against infection with non-encapsulated (F1-negative) strains. In an attempt to further optimize the F1-V elicited immune response and address efficacy concerns, we examined the inclusion of multiple toll-like receptor agonists into vaccine regimens. We examined the resulting immune responses and also any protection afforded to mice that were exposed to aerosolized Yersinia pestis. Our data demonstrate that it is possible to further augment the F1-V vaccine strategy in order to optimize and augment vaccine efficacy.

Electroacupuncture regulates the DREAM/NF-κB signalling pathway and ameliorates cyclophosphamide-induced immunosuppression in mice

2019 ◽  
Vol 37 (5) ◽  
pp. 292-300
Author(s):  
Zhihua Huang ◽  
Zhiping Hu ◽  
Juan Ouyang ◽  
Cheng Huang
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Regulatory Element ◽  
Interferon Γ ◽  
Signalling Pathway ◽  
Cell Toxicity ◽  
Immunosuppressed Patients ◽  
Factor Α ◽  
Immunosuppressed Mice

Background: Immune responses inhibit invasion by pathogens and antigens. Thus, it is important to promote the immune response in immunosuppressed patients. Objective: To examine whether electroacupuncture (EA) promotes the immune response by regulating the downstream regulatory element antagonist modulator / nuclear factor kappa B (DREAM/NF-κB) signalling pathway in a mouse model of cyclophosphamide (CP)-induced immunosuppression, and determine the most effective frequency. Methods: Twenty-four Kunming mice were intraperitoneally injected with CP to establish an immunosuppression model and six mice were injected with the same volume of normal saline as a control. The 24 mice were randomly divided into four groups: manual acupuncture, 2 Hz EA treatment, 100 Hz EA treatment and alternating 2/100 Hz EA treatment. After EA treatment for 3 days, immune response, natural killer (NK) cell toxicity and the expression of cytokines and DREAM/NF-κB were assessed. Results: EA treatment, especially at alternating 2/100 Hz frequency, improved spleen and thymus indices, increased lactate dehydrogenase and acid phosphatase levels, promoted concanavalin A- and lipopolysaccharide-induced splenocyte proliferation, increased NK cell toxicity and ameliorated CP-induced immunosuppression in mice. Additionally, 2/100 Hz EA treatment increased interleukin (IL)−2, IL-6, IL-12, tumour necrosis factor-α and interferon-γ levels and decreased IL-10 levels in CP-induced immunosuppressed mice. Finally, it was found that 2/100 Hz EA treatment increased p-IκBα and NF-κB expression and decreased DREAM and IκBα expression, suggesting that this treatment activates the NF-κB signalling pathway. Conclusion: 2/100 Hz EA treatment might be an effective way to enhance immune responses in CP-induced immunosuppressed mice.

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