adjuvant CpG 1018 / Dynavax - LARVOL DELTA

KA101 outperforms other clinical adjuvants in inducing balanced Th1/Th2 immunity and robust B cell responses to varicella-zoster virus glycoprotein E. (PubMed, Front Immunol) - "As TLR agonists, Poly(I:C) displayed a Th2-skewed profile with partial Th1 tendencies and exhibited oligoclonal B-cell expansion, whereas CpG 1018 potently promoted Th1 polarization and cytotoxic T-cell responses...Moreover, KA101 enhanced germinal center reactions, diversified the B-cell repertoire, and supported the establishment of long-term immune memory. Collectively, these findings provide mechanistic insights into adjuvant-antigen interactions and establish a rational framework for developing next-generation herpes zoster subunit vaccines with potent cellular and humoral immunogenicity and durable immune memory."

Journal • Herpes Zoster • Neuralgia • Pain • Varicella Zoster • IFNG

CpG 1018 augments mRNA vaccine-induced anti-tumor immunity by potentiating CD8+ T cell responses. (PubMed, Mol Ther Oncol) - "CpG 1018-adjuvanted mRNA vaccine induced transient body weight loss (<6%) with an overall good safety. Our data warrant further investigation of CpG 1018-adjuvanted neoantigen mRNA vaccine for potentially better tumor therapy."

Journal • Breast Cancer • Melanoma • Oncology • Pancreatic Cancer • Solid Tumor • CD4 • CD8 • GZMB • IFNG • TNFA

CpG-Adjuvanted Heplisav-B Induces Strong Th1-Biased Innate Responses Compared to Alum-Adjuvanted HBV Vaccines in PLWH (IMMUNOLOGY 2026) - "While Heplisav-B's CpG 1018 adjuvant improves immunogenicity in PLWH, its mechanisms for overcoming HIV-related immune dysfunction are not yet defined. We performed multiplex cytokine/chemokine profiling assays and high-dimensional flow cytometry, including markers to interrogate cellular metabolism, to characterize early innate responses 24 hours after the first dose of Engerix-B or Heplisav-B in PLWH who were non-responders to prior HBV vaccination. Heplisav-B induced robust early innate activation, characterized by significantly elevated IP-10, MCP-2, and IFN-γ versus baseline, consistent with Th1-skewed inflammatory profile that was not observed following Engerix-B vaccination. Heplisav-B induces stronger Th1-skewed innate responses and increased B cell frequency than Engerix-B in PLWH within the first 24 hours of vaccination, while overall cellular composition and activation remain largely preserved. These findings provide mechanistic insight into how..."

Clinical • Hepatitis B • Human Immunodeficiency Virus • Infectious Disease • CCL8 • IFNG • IL17A • IL2 • IL4 • TLR9

Optimizing T Cell Priming Using TLR4/9 Combination Adjuvant For Robust Cell-Mediated Immunity Against Influenza (IMMUNOLOGY 2026) - "Here, we investigated the potential of IVAX-1, a combination of TLR4 (MPLA) and TLR9 (CpG 1018) agonists formulated in a squalene oil-in-water emulsion (AddaVax), to mediate protection and generate CMI. We leveraged a murine H5N1 influenza model with fate-map reporters, conditional knock-out mice, multiphoton imaging, and flow cytometry to elucidate early spatiotemporal features of IVAX-1-driven immunity... By leveraging synergistic innate immune activation through multiple TLR pathways, the combination optimizes T cell priming without relying on antigen depot effects. Our findings identify key early innate immune events and cellular mediators that drive robust CMI and demonstrate the potential of TLR agonist combinations to elicit durable T-cell immunity."

Clinical • Infectious Disease • Influenza • Respiratory Diseases • IFNG • TLR4 • TLR9

A Phase 2, Randomized, Observer-Blind, Dose Finding Trial to Evaluate Safety and Immunogenicity of an Investigational Pandemic Flu Vaccine (ANZCTR) - P2 | N=180 | Active, not recruiting | Sponsor: PPD Australia PTY LTD

New P2 trial • Infectious Disease • Influenza • Respiratory Diseases

A Phase 1, Randomized, Observer-Blind, Dose Finding Trial to Evaluate Safety and Immunogenicity of an Investigational Pandemic Flu Vaccine (ANZCTR) - P1 | N=98 | Completed | Sponsor: PPD Australia PTY LTD

New P1 trial • Infectious Disease • Influenza • Respiratory Diseases

Clinical Trial of Recombinant Herpes Zoster Vaccine (CHO Cell) in Healthy Chinese Population Aged 40 Years and Older (clinicaltrials.gov) - P1/2 | N=960 | Active, not recruiting | Sponsor: Ab&B Bio-tech Co., Ltd.JS | Recruiting ➔ Active, not recruiting

Enrollment closed • Herpes Zoster • Varicella Zoster • CD40LG

HEPLISAV-B Breaks Immune Tolerance and Induces HBV Control via CD4 T Cell-Dependent Mechanisms in a Chronic Hepatitis B Mouse Model. (PubMed, bioRxiv) - "To evaluate the therapeutic efficacy and immunological mechanisms of HEPLISAV-B, a CpG-1018-adjuvanted HBsAg vaccine, in breaking immune tolerance and inducing functional cure-like responses in a murine model of CHB. The findings support its potential as a therapeutic vaccine in CHB patients. What is already known on this topic: Chronic HBV infection is marked by profound virus-induced immune tolerance, current antiviral therapies and vaccines fail to reliably induce HBsAg loss or restore effective antiviral immunity, highlighting the need for immune-based therapeutic strategies.What this study adds: This study demonstrates that the clinically approved vaccine HEPLISAV-B can break HBV immune tolerance in a chronic HBV mouse model, inducing durable HBsAg clearance and anti-HBs immunity, non-cytolytic depletion of intrahepatic HBV DNA, through a mechanism strictly dependent on CD4 T cells and CD40/CD40L signaling.How this study might affect research, practice or policy:..."

IO biomarker • Journal • Preclinical • Hepatitis B • Infectious Disease • Inflammation • CD4 • CD40LG • CD8

A narrative review of immune-mediated adverse events in clinical trials of CpG oligonucleotide toll-like receptor 9 agonists. (PubMed, Vaccine) - "We review and evaluate immune-mediated adverse events from three sets of clinical studies using toll-like receptor 9 (TLR9) agonists (CpG-ODN) as vaccine adjuvants and therapeutic agents in patients with cancer: 1) a comparison of immune-mediated adverse events across phase 1-3 clinical trials of the hepatitis B vaccine HEPLISAV-B (HepB-CpG) with the alum-adjuvanted hepatitis B vaccine (HepB-alum); 2) an analysis of the rates of immune-mediated adverse events across clinical trials of COVID-19 vaccines using the CpG 1018 adjuvant; and 3) the rates of immune-mediated conditions in a study of the CpG-ODN nelitolimod (SD-101) combined with the immune checkpoint inhibitor pembrolizumab in patients with advanced melanoma or head and neck cancer, compared with rates in historical studies of pembrolizumab monotherapy. Data evaluated in this review show no increased risk for potential autoimmune disorders with HepB-CpG or CpG 1018-adjuvanted COVID-19 vaccines. Combining CpG-ODN..."

Adverse events • Journal • Review • Head and Neck Cancer • Hepatitis B • Immunology • Infectious Disease • Melanoma • Novel Coronavirus Disease • Oncology • Solid Tumor • PD-1

VLA1601-102: Phase 1 Trial to Assess the Safety and Immunogenicity of an Inactivated, Adjuvanted Whole Zika Virus Vaccine Candidate (VLA1601) in Healthy Adults (clinicaltrials.gov) - P1 | N=150 | Completed | Sponsor: Valneva Austria GmbH | Active, not recruiting ➔ Completed

Trial completion • Infectious Disease

Dose-Dependent Efficacy of a Riboflavin and Ultraviolet Light-Inactivated Whole-Virion SARS-CoV-2 Vaccine in a Hamster Infection Challenge Model. (PubMed, Vaccines (Basel)) - "Here, we utilized the same animal model to evaluate the dose response to the vaccine candidate in combination with the adjuvant CpG1018. Flow cytometry revealed enhanced CD4+ Th1-biased responses in higher-dose groups. These findings demonstrate the protective efficacy of the SolaVAX SARS-CoV-2 vaccine candidate and support further evaluation of this vaccine production platform."

Journal • Preclinical • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CD4

Compatibility and Stability of a Shigella Polysaccharide-Protein Conjugate Antigen Formulated with Aluminum Salt and CpG 1018® Adjuvants. (PubMed, Vaccines (Basel)) - "In contrast, the glycoconjugate antigen and CpG adjuvant were both bound to the AH adjuvant and stable at 2-8 °C, pH 7.0. This AH-CpG formulation of the O-PS-IpaB conjugate antigens was identified as a promising candidate for future animal immunogenicity testing."

Journal • Infectious Disease

CIP2023-001: Safety and Immunogenicity of Innocell Autologous Cellular Immunotherapy for Recurrent Epithelial Ovarian Cancer (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: PhotonPharma, Inc. | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jun 2026 ➔ Dec 2026

Enrollment open • Trial primary completion date • Epithelial Ovarian Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor • BRCA • HRD

Innate Immunity Stimulation Via TLR9 in Early AD (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: NYU Langone Health | Trial primary completion date: Nov 2025 ➔ Nov 2026 | Trial completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Effect of Different Adjuvants on the Immunogenicity of a Recombinant Herpes Zoster Vaccine in Mice, Rats and Non-Human Primates. (PubMed, Vaccines (Basel)) - "The selected gE/SWE/CpG1018 combined with the adjuvant vaccine combination could effectively stimulate the humoral and cellular immune responses in SD rats and rhesus monkeys. The gE/SWE/CpG1018 combined with adjuvant vaccine may be a low-cost and highly effective vaccine candidate for the prevention of varicella zoster."

Journal • Preclinical • Herpes Zoster • Neuralgia • Pain • Varicella Zoster

Reconstruction of the lymphatic system by transplantation of a centrifuge-based bioengineered lymphatic tissue. (PubMed, Nat Commun) - "Lymph node-like structures composed of transplant- and host-derived cells, including immune cells, generate immune responses to an immunostimulant CpG1018. Here we show CeLyTs composed of lymphatic endothelial cells and MSCs reconstruct a lymph node and may represent a promising therapy for secondary lymphedema."

Journal • Oncology • Transplantation

Seroprotection of Hepb-Alum vs Hepb-Cpg Vaccines in People With HIV: A Meta-Analysis and Systematic Review (ACG 2025) - "HepB-CpG, which incorporates a Toll-like receptor 9 agonist (CpG 1018) as an adjuvant, has shown superior immunogenicity in the general population and is now being explored in PWH... Our meta-analysis included 459 participants (224 HepB-alum; 235 HepB-CpG). The pooled odds of achieving seroprotection ( defined as HBsAb ≥10 IU/L) were significantly higher with HepB-CpG compared to HepB-alum (OR 5.34; 95% CI: 1.71–16.65; p=0.004), with moderate heterogeneity (I² = 66%). In subgroup analysis, absence of diabetes was associated with higher seroconversion (84.1%), while rates were comparable in participants with chronic kidney disease, prior use of steroids or biologics."

Retrospective data • Review • Chronic Kidney Disease • Diabetes • Hepatitis B • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Inflammation • Metabolic Disorders • Nephrology • Renal Disease

A CpG 1018S/QS-21-Adjuvanted HBsAg Therapeutic Vaccine as a Novel Strategy Against HBV. (PubMed, Vaccines (Basel)) - "These responses collectively contributed to the reversal of T cell exhaustion and breakdown of immune tolerance, facilitating sustained viral suppression. Our findings demonstrate that the CpG 1018S/QS-21-adjuvanted vaccine induces potent humoral and cellular immunity against chronic HBV infection and represents a promising candidate for clinical chronic HBV (CHB) treatment."

IO biomarker • Journal • Hepatitis B • Infectious Disease • Inflammation • CD4 • CD8 • HAVCR2 • IL21 • TIGIT • TNFA

CD4-DEPENDENT MECHANISMS DRIVE HEPLISAV-B MEDIATED HBSAG CLEARANCE AND ANTI-HBV IMMUNITY IN CHRONIC HBV CARRIER MICE (AASLD 2025) - "HEPLISAV-B, an FDA-approved HBV vaccine combining HBsAg with the TLR9 agonist CpG-1018, has demonstrated superior immunogenicity clinically. HEPLISAV-B effectively breaks immune tolerance in chronic HBV infection, leading to stable HBsAg clearance, suppressed viral production, and robust, durable anti-HBV humoral and cellular immunity. Our findings unequivocally demonstrate that CD4 T cells are critically essential for mediating these therapeutic effects. These results highlight HEPLISAV-B's strong potential as a promising therapeutic vaccine candidate for achieving functional cure in patients with chronic HBV infection."

IO biomarker • Preclinical • Hepatitis B • Hepatology • Infectious Disease • CD4 • CD8 • IFNG • PTPRC • TNFA

Innate and T-cellular immune responses to sequential vaccination with chimeric hemagglutinin split influenza virus vaccines in mice. (PubMed, Vaccine) - "Here we provide an in-depth characterization of the innate immune response and antigen-specific T-cellular immune response in mice after sequential immunization with the group 2 cH15/3HK14N2HK14 and cH4/3HK14N2HK14 virus vaccine candidates with or without CpG 1018 adjuvant and during a heterologous virus challenge...Passive transfer of T-cells from immunized to naïve mice did not reduce weight loss and viral replication but affected the innate immune cell population dynamics and cytokine response in mouse lungs after the challenge. The depletion of CD4+ T-cells did not affect viral replication in mouse lungs but influenced cytokine production and innate immune cell population dynamics."

Journal • Preclinical • Infectious Disease • Influenza • Oncology • Respiratory Diseases • CD4 • IFNG • IL10 • IL13 • IL2 • IL4 • IL5 • TNFA

Immune responses to a heterologous booster with mRNA based COVID-19 vaccine after priming with an inactivated Newcastle disease virus recombinant vaccine expressing the SARS-CoV-2 spike protein (NDV-HXP-S). (PubMed, Vaccine) - "The immune responses stimulated by the heterologous boost with bivalent mRNA vaccine in the NDV-HXP-S primed groups were high especially among the hybrid immune subgroup. Thai Clinical Trial Registry: WHO REGISTRY PLATFORM- TCTR20230809003."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • IFNG

Multivalent COBRA Hemagglutinin and Neuraminidase Influenza Vaccines Adjuvanted with TLR9 Agonist CpG 1018. (PubMed, Vaccines (Basel)) - "Overall, CpG 1018 adjuvanted COBRA HA/NA elicited enhanced protective antibodies compared to the unadjuvanted vaccine against several drifted H1N1 and H3N2 influenza viruses in pre-immune mice that were either intramuscularly or intranasally vaccinated with a balanced Th1/Th2 immune response."

Journal • Infectious Disease • Influenza • Respiratory Diseases

Immunogenicity and cellular response of a herpes zoster virus gEgI fusion protein adjuvanted with CpG-emulsion in mice. (PubMed, J Nanobiotechnology) - "Furthermore, we introduced a composite adjuvant, an emulsion-type adjuvant combined with CpG1018 (XUA09C), which was shown to enhance both humoral and cellular immune responses beyond the capabilities of XUA09 with CpG alone. Single-cell RNA sequencing highlighted that gEgI/XUA09C more effectively promotes early immune activation, B and T cell proliferation, and memory T cell augmentation compared to Shingrix. These findings position the XUA09C-adjuvanted gEgI as a promising candidate for further development in HZ vaccine strategies, potentially better serving the needs of the immunocompromised population."

Journal • Preclinical • Herpes Zoster • Infectious Disease • Varicella Zoster • CD4

Study to Evaluate the Safety and Immunogenicity of an HIV-1 Vaccine Regimen of Adjuvanted UVAX-1107 Followed by Adjuvanted UVAX-1107 or Adjuvanted UVAX-1197 in Healthy Subjects Aged 25-55 Years. (clinicaltrials.gov) - P1 | N=34 | Completed | Sponsor: Uvax Bio LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Hepatitis B vaccination with HepB-CpG in people living with HIV: a narrative review. (PubMed, Expert Rev Vaccines) - "This review explores recent research on the two-dose HepB-CpG (HEPLISAV-B) vaccine, which is a potential solution to the challenge of suboptimal immune responses to three-dose HBV vaccines (HepB-alum) in people living with HIV (PLWH)...HepB-CpG might be more immunogenic in vaccine-naive and vaccine-experienced PLWH. Both attributes make HepB-CpG a possible future standard of care for adult HBV vaccination in PLWH."

Journal • Review • Fibrosis • Hepatitis B • Human Immunodeficiency Virus • Immunology • Infectious Disease • Inflammation • Liver Cancer • Liver Cirrhosis • Oncology • Solid Tumor