TVGV-HB / Thevax Genetics Vaccine - LARVOL DELTA

Generation of a shelf-stable, broadly-reactive influenza vaccine formulated with TLR4, TLR7/8, or TLR9 stimulating adjuvants. (PubMed, Vaccine) - "Influenza H1 and H3 hemagglutinin proteins based upon the computationally-optimized broadly-reactive antigen (COBRA) methodology were mixed with one of three toll-like receptor (TLR) agonists, CpG1826 (TLR9 agonist), INI-2002 (TLR4 agonist), or INI-4001 (TLR7/8 agonist)...However, all vaccinated ferrets from these groups were protected against an H1N1 influenza virus challenge, irrespective of the adjuvant. Overall, the constituted vaccines used following the TFF process were effective at eliciting protective immune responses following intranasal administration to ferrets."

Journal • Infectious Disease • Influenza • Respiratory Diseases • TLR4 • TLR7 • TLR9

Toll-like Receptor 9 on Donor RBCs Enhances Transfusion Induced Alloimmunity in Mice (AABB 2025) - "Prior to transfusion, mice were treated with either CpG (ODN 1826) or PBS (vehicle control)... TLR9 expressed on RBCs plays a mechanistic role in enhancement of alloimmunization to transfused RBCs by CpG, which is a model for recipient inflammation in response to microbial infection. Because no effect was observed when TLR9 was selectively eliminated from recipient RBCs, we conclude that the role of TLR9 is not a general RBC role but is particular to the transfused RBCs expressing alloantigen. CpG is known to act on TLR9 expressed by B cells to enhance activation and differentiation if the B cell receptor (BCR) is simultaneously engaged."

Preclinical • Infectious Disease • Inflammation • TLR9

Multifunctional HBc Virus-Like Particles Reprogram Immunosuppressive Macrophages and Potentiate CD8+ T Cell Responses for Enhanced Cancer Immunotherapy. (PubMed, Int J Nanomedicine) - "Immunostimulatory CpG oligodeoxynucleotide 1826 (CpG) was encapsulated within VLP...To the best of our knowledge, this is the first nanovaccine architecture to enable coordinated immunomodulation. Its modular design supports the clinical translation of solid tumors and personalized immunotherapy."

IO biomarker • Journal • Hepatitis B • Immunology • Infectious Disease • Melanoma • Oncology • Solid Tumor • CD276 • CD4 • CD69 • CD8 • CD86 • GZMB • MRC1

CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/itaconate metabolic pathway. (PubMed, Mol Med) - "CpG ODN alleviated liver injury induced by APAP through the activation of the TLR9/NF-κB signaling pathway in macrophages, upregulating the expression of IRG1 protein, promoting the production of endogenous metabolite itaconate, and inhibiting macrophage apoptosis which was regulated by upregulating the expression of Nrf2 to inhibit ROS production. This study sheds new light on CpG ODN as a therapeutic strategy in resistance to APAP-induced liver injury."

Journal • Hepatology • Liver Failure • Metabolic Disorders

Inhibition of Aspartate β-Hydroxylase Enhances Anti-Tumor Immunity. (PubMed, Immunotargets Ther) - "ASPH inhibition did not reduce tumor growth or promote the anti-tumor effect of innate immunity stimulation with the synthetic oligonucleotide ODN1826, but it significantly enhanced tumor growth reduction induced by DNA vaccination...Different types of lymphoid and myeloid cells were likely involved in the activated immune response that was efficient against tumors with MHC-I downregulation, which are often resistant to T-cell-based therapies. Due to different types of activated immune cells, ASPH inhibition could improve immunotherapy for tumors with various MHC-I expression levels."

IO biomarker • Journal • Oncology • ASPH • CD8

Platelets contribute to organ damage in a mouse model of an interferon-gamma-driven cytokine storm (ISTH 2025) - "Methods An IFNγ-driven cytokine storm was induced in mice by repeated administration of the TLR9 agonist CpG ODN-1826...Histology revealed numerous microthrombi with associated necrotic and inflammatory damage in lung and liver but not in brain or kidney. Thrombocytopenic PF4-iCre+xiDTR+/+ mice showed significantly reduced microthrombus-associated liver and lung damage but no change in weight loss or cytopenia."

Cytokine storm • Preclinical • Infectious Disease • IFNG • LAMP1 • SELP

Co-assembled Manganese-CpG Nanoliposomes for Enhanced Immunotherapy against Colon Cancer Stem Cells. (PubMed, Adv Healthc Mater) - "In vivo treatment with Mn@CpG@NLP significantly inhibited tumor growth and prolonged survival in a mouse model. This study highlights the potential of nano-adjuvant platforms in immunotherapy targeting cancers driven by colon CSCs."

Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Differential innate immune activation by four different CpG-ODNs in porcine and murine cells: Implications for vaccine design. (PubMed, Res Vet Sci) - "Notably, CpG-ODN 1826 exhibited species-specific activity in mice, inducing IL-6, IL-12p40, IFN-β, and IFN-γ. These findings reveal significant interspecies differences in CpG-ODN-induced immune responses, emphasizing the importance of species-specific considerations when selecting CpG-ODNs as vaccine adjuvants for preclinical and veterinary applications."

Journal • Preclinical • IFNB1 • IFNG • IL6 • TLR9

Dual prophylactic and therapeutic potential of iPSC-based vaccines and neoantigen discovery in colorectal cancer. (PubMed, Theranostics) - "CpG oligonucleotide (ODN) 1826 served as a vaccine adjuvant... Our findings reveal potential mechanisms underlying the efficacy of iPSC-based vaccines in cancer immunotherapy. Additionally, HNRNPU and NCL were identified as key antigen proteins in iPSC, demonstrating promise for the development of peptide-based vaccines for both the prevention and treatment of CRC."

IO biomarker • Journal • Colorectal Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • CD8 • NCL

Elucidating the systemic humoral response and immune microenvironment at the implant interface of the Vaccine Platform for Extended Antigen Release (VPEAR) (IMMUNOLOGY 2025) - "Description The Vaccine Platform for Extended Antigen Release (VPEAR) is an implantable device with a polyanhydride depot that sustains the release of the model antigen ovalbumin (OVA) and the adjuvant CpG ODN 1826 for over 24 weeks...Preliminary qPCR data show elevated CXCL13 expression, critical for B-cell zone formation, and CCL5, a recruiter of T cells and monocytes, but no upregulation of CCL21, which is associated with T-cell zones. These findings suggest VPEAR elicits a robust humoral response with sustained B-cell activity at the cap, which may be consistent with a B-cell-dominated tertiary lymphoid structure.Keywords: Animals Rodent; Cells B Cells; Molecules Antibodies Chemokines Cytokines"

Late-breaking abstract • CCL21 • CXCL13

Effects of Xiaozhi Huaxian Formula on Promoting Recompensation in Mice with MASH-related Cirrhosis Receiving BM-MSCs Transplantation Treatment (APASL 2025) - "CpG ODN 1826 stimulated primary liver cells in vitro, cells supernatant was extracted, the levels of IL-1β, IL-6 and TNF-α were determined by ELISA... XHF can promote the effects of BM-MSCs transplantation on recompensation in MASH-related cirrhosis. The mechanism is associated with the down-regulation of TLR9/NF-κB signaling pathway expression and activation, the inhibition of inflammatory cytokines secretions and the improvement of liver inflammatory microenvironment. *Corresponding authors: Xin Wang and Limin Tian."

Preclinical • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Metabolic Dysfunction-Associated Steatohepatitis • Transplantation • IL1B • IL6 • MYD88 • TNFA • TRAF6

Immunogenicity and efficacy in mice of two adjuvant formulations based on the C -and N-terminus of merozoite surface protein 1 of Plasmodium yoelii. (PubMed, Vaccine) - "In this study, the N- and C-terminal fragments of the PyMSP-1 (PyMSP-1 N and PyMSP-1C) were immunized to mice with either incomplete Freund's adjuvant (IFA) plus CpG ODN 1826 or Aluminum salts (Alum) plus CpG, followed by a challenge with Plasmodium yoelii 17XNL to investigate vaccine efficacy...In conclusion, the N-terminal fragment of PyMSP-1 protected mice although it showed lower humoral and cellular immune response compared to C-terminal of MSP-1 in IFA plus CpG. The antibody level of PyMSP-1 N was comparable to that of PyMSP-1C when it was formulated with IFA plus CpG."

Journal • Preclinical • Infectious Disease • Malaria • CD4 • CD8 • IFNG

Context-Dependent Impact of Tumor-Infiltrating B Cells in High-Risk Prostate Cancer and Head and Neck Cancer (ASTRO 2024) - "In this context, a single arm prospective study (PROTUX), was previously performed using neoadjuvant rituximab to deplete B cells in patients with HR-PCa prior to prostatectomy...In vivo therapeutics include anti-PD-L1 mAB (10F.9G2), anti-CD40 mAB (FGK4.5), and TLR9 agonist (ODN 1826)... Analysis of human samples from PROTUX trial demonstrated that B cell depletion impacts T cell infiltration, clonality, and phenotype. Furthermore, B cell-directed immunotherapies in tumor models improved local control. Given the increasing appreciation for crosstalk between T cells and B cells in mediating anti-tumor immune responses, these findings demonstrate a context and tumor-type dependent role for B-cells in cancer."

Genito-urinary Cancer • Head and Neck Cancer • Oncology • Prostate Cancer • Solid Tumor • Squamous Cell Carcinoma of Head and Neck • TRB

Evaluation of the adjuvant effect of imiquimod and CpG ODN 1826 in chimeric DNA vaccine against Japanese encephalitis. (PubMed, Int Immunopharmacol) - "Furthermore, it played a regulatory and optimizing role in subsequent antigen-specific immune responses, resulting in effective cellular and humoral immunity and providing prolonged immune protection. The synergistic effect of IMQ and CpG ODN 1826 as adjuvants offers a novel approach for the development of Japanese encephalitis nucleic acid vaccines."

Journal • CNS Disorders • Infectious Disease

Supramolecular Assembly of Polycation/mRNA Nanoparticles and In Vivo Monocyte Programming (ASGCT 2024) - "Particles with effective monocyte transfection were loaded with control (mLuc) or ovalbumin (mOVA) encoding mRNA with/without CpG ODN1826 (ODN), a Toll-like receptor 9 agonist, and administered to C57BL/6 mice to evaluate anticancer immune activation in a melanoma model. Submicron PBAE/mRNA particles were formulated by kinetic assembly and stabilized between 100 and 900 nm (Fig... Kinetic assembly of PBAE/mRNA particles enables the controllable and scalable production of stable submicron (200-1000 nm) particles. 400-nm submicron particles effectively delivered mRNA and adjuvant to phagocytes, particularly circulating monocytes, in vivo. Transfected circulating monocytes can be programmed for activation as antigen-presenting cells leading to antigen-specific T cell activation."

IO biomarker • Preclinical • Gene Therapies • Infectious Disease • Melanoma • Oncology • Solid Tumor

Extracellular vesicles derived from plasmodium-infected red blood cells alleviate cerebral malaria in plasmodium berghei ANKA-infected C57BL/6J mice. (PubMed, Int Immunopharmacol) - "C57BL/6J mice were intravenously immunized with EVs (EV-I.V. + CM group) or subcutaneously vaccinated with the combination of EVs and CpG ODN-1826 (EV + CPG ODN-S.C. + CM group) on days 0 and 20, followed by infection with Plasmodium berghei ANKA (P.bANKA) on day 20 post-second immunization...The protective effects were determined by immunological pathways and brain targets elicited by EVs. Intravenous immunization exhibited better performance than subcutaneous immunization, which perhaps correlated with EVs, which can naturally cross BBB to play a better role in brain protection."

Journal • Preclinical • Infectious Disease • Inflammation • Malaria

Evaluation of different types of adjuvants in a malaria transmission-blocking vaccine. (PubMed, Int Immunopharmacol) - "In this study, we formulated a promising TBV candidate antigen, the P. berghei ookinete surface antigen PSOP25, with different types of adjuvants, including the TLR4 agonist monophosphoryl lipid A (MPLA), the TLR9 agonist cytosine phosphoguanosine oligodeoxynucleotides (CpG ODN 1826) (CpG), a saponin adjuvant QS-21, aluminum hydroxide (Alum), and two combination adjuvants MPLA + QS-21 and QS-21 + CpG...PSOP25 induced a higher number of Tfh cells in splenocytes when combined with MPLA, CpG, and QS-21 + CpG; and there was no increase in these cell populations when PSOP25 was administered with Alum. In conclusion, CpG may confer enhanced efficacy for the rPSOP25 vaccine, as evidenced by the ability of the elicited antisera to induce protective immune responses and improved transmission-blocking activity."

Journal • Infectious Disease • Malaria • IFNG • TLR4 • TNFA

Immunotherapy with STING and TLR9 agonists promotes synergistic therapeutic efficacy with suppressed cancer-associated fibroblasts in colon carcinoma. (PubMed, Front Immunol) - "In this study, we investigated the immunotherapeutic effects of ADU-S100 as a STING agonist and CpG ODN1826 as a TLR9 agonist in a preclinical model of colon carcinoma. Remarkably, the significant downregulation of CAFs in the TME indicated that suppression of tumorigenesis occurred after immunoadjuvant therapy. The results illustrate the potential of targeting the STING and TLR9 pathways as powerful immunoadjuvants in the treatment of preclinical colon carcinoma and the possibility of harnessing these pathways in future therapeutic approaches."

IO biomarker • Journal • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor • CAFs • STING

Toll-like Receptor Ligands Enhance Vaccine Efficacy against a Virulent Newcastle Disease Virus Challenge in Chickens. (PubMed, Pathogens) - "In this study, birds were vaccinated intranasally with a live LaSota strain with or without imiquimod or ODN-1826 (50 µg/bird). A differential expression of antiviral and immune-related genes was observed among groups from tissues (Harderian gland, trachea, cecal tonsil, and spleen) collected 1 and 3 days after treatment. These results demonstrate the potential of TLR-targeted adjuvants as mucosal vaccine enhancers and warrant a further characterization of immune correlates and optimization for efficacy."

IO biomarker • Journal • TLR2 • TLR7 • TLR9

The effect of Toll-like receptor agonists on the immunogenicity of MVA-SARS-2-S vaccine after intranasal administration in mice. (PubMed, Front Cell Infect Microbiol) - "We intranasally immunized C57BL/6 mice with MVA-SARS-2-S vaccine in the presence of either TLR3 agonist polyinosinic polycytidylic acid [poly(I:C)], TLR4 agonist bacterial lipopolysaccharide (LPS) from Escherichia coli, or TLR9 agonist CpG oligodeoxynucleotide (CpG ODN) 1826...Particularly TLR3 agonists hold a promise to potentiate MVA-induced cellular immune responses. On the other hand, additional research is necessary to identify optimal combinations of agonists that could enhance MVA-induced humoral responses."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD8 • CD86 • TLR4

Lipid Nanoparticle Delivery Alters The Adjuvanticity of The TLR9 Agonist Cpg by Innate Immune Activation in Lymphoid Tissue. (PubMed, Adv Healthc Mater) - "We report on the formulation of class B CpG ODN1826 in lipid nanoparticles (LNPs) containing an ionizable cationic lipid that complexes CpG through electrostatic interaction...Unformulated, soluble, CpG, by contrast, is unable to induce robust innate activation in draining lymph nodes and is distributed systemically. In a vaccination setting, LNP-formulated CpG, admixed with a protein antigen, induces higher antigen-specific antibody titers and T cell responses than antigen admixed with unformulated soluble CpG."

Journal • Hepatology • Infectious Disease • Oncology

Yang-Xin-Shu-Mai granule alleviates atherosclerosis by regulating macrophage polarization via the TLR9/MyD88/NF-κB signaling pathway. (PubMed, J Ethnopharmacol) - "YXSMG can reduce the level of blood lipid and improve the size of atherosclerotic plaque and inflammatory infiltration in ApoE mice fed with high fat. It is concluded that YXSMG can improve the mechanism of atherosclerotic plaque by inhibiting TLR9/MyD88/NF-κB pathway reprogramming macrophage M1/M2 polarization and reducing arterial inflammation."

IO biomarker • Journal • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Heart Failure • Inflammation • APOE • MYD88

Validation of Multi-epitope Peptides Encapsulated in PLGA Nanoparticles Against Influenza A Virus. (PubMed, Pharm Res) - "The study demonstrated the self-adjuvanting properties of the PLGA nanoparticles as a delivery system without the need for incorporation of toxic and costly conventional adjuvants in multi-epitope peptide-based vaccines."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Pyroptosis induced by TLR9 ligand, ODN1826, requires ROS production and caspase-11 activation in Raw264.7 cells. (PubMed, Asian Pac J Allergy Immunol) - "ODN1826 induces pyroptosis in Raw264.7 cells via caspase-11 and GSDMD activation. Moreover, the production of ROS by this ligand plays an essential role in the regulation of caspase-11 and GSDMD activation, which then controls pyroptosis in TLR9 activation."

IO biomarker • Journal • Inflammation • TLR9

The potential role of CpG oligodeoxynucleotides on diabetic cardiac autonomic neuropathy mediated by P2Y12 receptor in rat stellate ganglia. (PubMed, Int Immunopharmacol) - "Overall, CpG-ODN 1826 alleviates the sympathetic excitation and abnormal neuron-glial signal communication via activating TLR9 receptors to achieve a balance of autonomic activity and relieve the DCAN in rats. The mechanism may involve the regulation of P2Y12 receptor in SG by reducing ATP release and NF-κB expression, which counteract neuroinflammation and ferroptosis mediated by activated P2Y12 in SG."

IO biomarker • Journal • Preclinical • Cardiovascular • Diabetes • Diabetic Neuropathy • Inflammation • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus • GPX4 • IL1B • NCOA4 • NF-κβ • TNFA