Small molecule modulators of immune pattern recognition receptors

Tsukidate, Taku; Hespen, Charles W.; Hang, Howard C.

doi:10.1039/d3cb00096f

Cited by 7 publications

(3 citation statements)

References 269 publications

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“…For instance, bacterial cell wall preparations containing peptidoglycan, known to activate NOD1 and NOD2, and substances like aluminum hydroxide, shown to activate the NLRP3 inflammasome, have been used as adjuvants. 43 , 44 This new understanding of NLRs in adjuvant action provides valuable insights for developing vaccines, highlighting their role in enhancing vaccine efficacy through specific immune pathway activation.…”

Section: Discussionmentioning

confidence: 99%

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Li,

Zhang,

Lin

et al. 2024

JIR

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Purpose The rapid global spread of the SARS-CoV-2 Omicron variant introduces a novel complication: the emergence of IBD (inflammatory bowel disease)-like ulcers in certain patients. This research delves into this new challenge by juxtaposing the clinical manifestations and genetic expression patterns of individuals affected by the Omicron variant of COVID-19 with those diagnosed with IBD. It aims to decode the link between these conditions, potentially shedding light on previously unexplored facets of COVID-19 pathophysiology. This investigation emphasizes gene expression analysis as a key tool to identify wider disease correlations and innovative therapeutic avenues. Patients and Methods From March to December 2022, patients with SARS-CoV-2 Omicron infection and inflammatory bowel disease and healthy controls were recruited in Shanghai East Hospital, Shanghai, China. The epidemiological and clinical characteristics of the patients were compared. Four RNA sequencing datasets (GSE205244, GSE201530, GSE174159, and GSE186507) were extracted from the Gene Expression Omnibus database to detect mutually differentially expressed genes and common pathways in patients with SARS-CoV-2 infection and inflammatory bowel disease. Results Compared to patients with active inflammatory bowel disease, patients with SARS-CoV-2 infection were more likely to have elevated interferon-α levels and an increased lymphocyte count and less likely to have high interleukin-6, tumor necrosis factor-α, and C-reactive protein levels and an elevated neutrophil count. A total of 51 common differentially expressed genes were identified in the four RNA-sequencing datasets. Enrichment analysis suggested that these genes were related to inflammation and the immune response, especially the innate immune response and nucleotide oligomerization domain-like receptor signaling pathway. Conclusion The inflammation and immune-response pathways in COVID-19 and inflammatory bowel disease have several similarities and some differences. The study identifies the NLR signaling pathway’s key role in both COVID-19 and IBD, suggesting its potential as a target for therapeutic intervention and vaccine development.

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Section: Discussionmentioning

confidence: 99%

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Li,

Zhang,

Lin

et al. 2024

JIR

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“…In other words, by mimicking the signals associated with infection or tissue damage, these compounds can enhance the immune response against solid cancers, offering a new paradigm in cancer treatment, including HPV-associated cancer. [144][145][146][147][148] Below, we summarize the recent findings on the novel interventions designed to enhance our body's ability to recognize and eliminate HPV-infected/transformed cells through PRR agonists.…”

Section: Pattern Recognition Receptor Agonists Against Hpv-induced Ca...mentioning

confidence: 99%

High‐risk HPV oncoproteins E6 and E7 and their interplay with the innate immune response: Uncovering mechanisms of immune evasion and therapeutic prospects

Lo Cigno,

Calati,

Girone

et al. 2024

Journal of Medical Virology

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Human papillomaviruses (HPVs) are double‐stranded DNA (dsDNA) tumor viruses causally associated with 5% of human cancers, comprising both anogenital and upper aerodigestive tract carcinomas. Despite the availability of prophylactic vaccines, HPVs continue to pose a significant global health challenge, primarily due to inadequate vaccine access and coverage. These viruses can establish persistent infections by evading both the intrinsic defenses of infected tissues and the extrinsic defenses provided by professional innate immune cells. Crucial for their evasion strategies is their unique intraepithelial life cycle, which effectively shields them from host detection. Thus, strategies aimed at reactivating the innate immune response within infected or transformed epithelial cells, particularly through the production of type I interferons (IFNs) and lymphocyte‐recruiting chemokines, are considered viable solutions to counteract the adverse effects of persistent infections by these oncogenic viruses. This review focuses on the complex interplay between the high‐risk HPV oncoproteins E6 and E7 and the innate immune response in epithelial cells and HPV‐associated cancers. In particular, it details the molecular mechanisms by which E6 and E7 modulate the innate immune response, highlighting significant progress in our comprehension of these processes. It also examines forward‐looking strategies that exploit the innate immune system to ameliorate existing anticancer therapies, thereby providing crucial insights into future therapeutic developments.

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“…New analytical methods to address these challenges are rapidly surging in the field. [24][25][26][27][28][29] Gas chromatography (GC) and high-performance liquid chromatography (HPLC) are commonly used separation techniques employed for lipids and adjuvants. GC can be used to characterize volatile components, whereas appropriate sample preparation is required for non-volatile components.…”

Section: Introductionmentioning

confidence: 99%

Digitally Enabled Generic Analytical Framework Accelerating the Pace of Liquid Chromatography Method Development for Vaccine Adjuvant Formulations

Hemida,

Barrientos,

Kinsey

et al. 2024

Preprint

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The growing use of adjuvants in the fast-paced formulation of new vaccines has created an unprecedented need for meaningful analytical assays that deliver reliable quantitative data from complex adjuvant and adjuvant-antigen mixtures. Due to their complex chemical and physical properties, method development for the separation of vaccine adjuvants is considered a highly challenging and laborious task. Reversed-phase liquid chromatography (RPLC) is among the most important tests in the (bio)pharmaceutical industry for release and stability indicating measurements including adjuvant content, identity, and purity profile. However, the time constraints of developing “on-demand” robust quantitative methods prior to each change in formulation can easily lead to sample analysis becoming a bottleneck in vaccine development. Herein a simple and efficient generic analytical framework capable of chromatographically resolving the most commonly used non-aluminum based adjuvants across academic and industrial sectors is introduced. This was designed to seek a more proactive approach for fast-paced assay development endeavors that evolved from extensive stationary phase screening in conjunction with multifactorial in silico simulations of adjuvant retention time (RT) as a function of gradient time, temperature, organic modifier blending, and buffer concentration. The multifactorial retention models yield 3D resolution maps with excellent baseline separation of all adjuvants in a single run, which was found to be very accurate, with differences between experimental and simulated retention times of less than 1%. The analytical framework described here also includes the introduction of a more versatile approach to method development by introducing a dynamic RT database for adjuvants covering the entire library of adjuvants with broad mechanisms of action across numerous vaccine formulations with excellent linearity, accuracy, precision, and specificity. The power of this framework was also demonstrated with numerous analytical assays that can be generated rapidly from simulations guiding vaccine processes in the development of new adjuvant formulations. Analytical assay in this work covers content, purity profile by RPLC-UV-CAD, and component identification (RPLC-MS) across complex vaccine formulations, including the use of surfactants (e.g., polysorbates), as well as their separation from adjuvant targets.

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Small molecule modulators of immune pattern recognition receptors

Abstract: In this review article, we summarize exciting developments in discovery and characterization of small molecule PRR modulators and highlight opportunities for chemical biology and therapeutic discovery.

Cited by 7 publications

References 269 publications

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

Shared Immune Associations Between COVID-19 and Inflammatory Bowel Disease: A Cross-Sectional Observational Study in Shanghai, China

High‐risk HPV oncoproteins E6 and E7 and their interplay with the innate immune response: Uncovering mechanisms of immune evasion and therapeutic prospects

Digitally Enabled Generic Analytical Framework Accelerating the Pace of Liquid Chromatography Method Development for Vaccine Adjuvant Formulations

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