Table 1.
Summary of immunomodulatory agents in clinical trials targeting HBV.
| Compound Name | Class | Mechanism of Action | Clinical Phase | Effects on HBsAg/HBeAg | Other Data | Status | References |
|---|---|---|---|---|---|---|---|
| Innate Immunity Activators | |||||||
| TLR7 (GS-9620, Gilead Sciences) | Small molecule | TLR7 | II | No HBsAg decline in patients | Lack of effect on cccDNA in vitro. Dose-dependent induction of ISG15, NKs, and HBV-specific T cell response | Ongoing | [77,78,79,80] |
| TLR8 (GS-9688, Gilead Sciences) | Small molecule | TLR8 | II | Decline in HBsAg levels or HBeAg loss at 24 weeks | Dose-dependent induction of IL-12, IL-18, TNF-α, and IFN-λ | Ongoing | [81] |
| RIG-I agonist (SB-9200, Springbank) | Small molecule | RIG-I | II | - | Dose-dependent antiviral response against HBV DNA and HBV RNA | Ongoing | [82] |
| Thymosin α1 (ZADAXIN, SciClone Pharmaceuticals) | Peptide | - | IV | Eliminated both HBsAg and HBeAg in select patients | Strong immune response | Ongoing | [83] |
| Adaptive Immunity Activators | |||||||
| PD-1 inhibitor (Nivolumab, Opdivo, Bristol-Myers Squibb) | Monoclonal antibody | PD-1:PD-L1 inhibitor | I | Decrease in HBsAg titers | Single dose of Nivolumab (with or without GS4774) | Ongoing | [84] |
| GS-4774 (Gilead Sciences) | Heat-inactivated, yeast protein-based therapeutic vaccine (expressing HBsAg, HBcAg, HBx) | Vaccine | II | No significant reduction in HBsAg | Safe and well-tolerated | Discontinued | [85,86,87] |
| DV-601 (Dynavax Technologies) | Protein-based vaccine (containing HBsAg and HBcAg) | Vaccine | I | - | Produced antiviral response | Terminated | [88,89] |
| HepTcell (Altimmune) | Composed of nine peptides from highly conserved regions of HBV polymerase, core, and surface antigens | Vaccine | I | No effect on HBsAg | Well-tolerated, increased T cell responses against HBV over baseline compared to placebo | Ongoing | [90] |
| TG1050 (Transgene) | Adenovirus 5-based therapeutic vaccine expressing three HBV proteins (polymerase, core, and surface antigen) | Vaccine | I | - | Good safety profile, induced HBV-specific cellular immune response | Ongoing | [91] |
| AIC649 (AiCuris) | Inactivated parapoxvirus (iPPVO) preparation | Vaccine | I | - | Well-tolerated, increased IL-1β, IL-6, IL-8, IFN-γ and reduced IL-10 plasma levels | Ongoing | [92] |
| pCMV-S2.S (Institut Pasteur, France) | DNA-based vaccine encoding HBV small (S) and middle (preS2 +S) envelope proteins | Vaccine | I/II | - | Well-tolerated, activated or restored T cell responses in some CHB carriers, weak and transitory: incapable of controlling anti-HBV immune response recurrence and recovery |
Ongoing | [93,94] |
| INO-1800 (Inovio) | Adenoviral-based DNA vaccine, encodes S1/S2/S envelope gene, core, polymerase sequences, X proteins and human IL-12 as adjuvant | Vaccine | I | - | Activated and expanded CD8+ killer T cells | Terminated | [88,95] |
| HB-110 (Genexine, Inc.) | Second-generation therapeutic HBV adenoviral-based DNA vaccine encoding S, L, core, polymerase protein, adjuvanted with IL-1 | Vaccine | I | HBeAg seroconversion | Well-tolerated, induced weaker HBV-specific T cell responses in Korean patients than in Caucasian patients | Ongoing | [96] |