Meiji Holdings · · Recombinant Proteins
hepatitis-B vaccine is a recombinant proteins developed by Meiji Holdings. It is approved for therapeutic indications via injectable (others) or subcutaneous injection.
| Company | Meiji Holdings |
| Drug Class | Recombinant Proteins, Vaccine |
| Route | Injectable (Others), Subcutaneous Injection |
| Status | Approved |
hepatitis-B vaccine acts on 1 molecular target:
| (S) |
hepatitis-B vaccine is developed for 1 unique indication across 1 therapeutic area.
| Therapeutic Area | Condition | Phase |
|---|---|---|
| Infections and infestations | Hepatitis B | ✓ Approved |
Madaeng Thanawat T, Soponkanaporn Sirisucha S, Tangnararatchakit Kanchana K, Apiwattanakul Nopporn N et al.
Chen Shuling S, Wang Yuanqi Y, Chen Jingying J, Xie Wenxuan W et al.
The prevailing notion is that effector T cell activation mediates anti-PD-1 efficacy in cancer. Here, we conducted a mechanistic study parallel to our phase 2 trial of perioperative anti-PD-1 therapy in patients with resectable recurrent hepatocellular carcinoma (HCC) (NCT04615143) to study its mechanism of action. Late-recurrence patients present two distinct subtypes characterized by T cell or B cell dominant responses in the tumor microenvironment by dynamic single-cell multi-omics analysis. Clonal antibody repertoire analysis and spatially paired scRNA-seq/BCR-seq reveal somatic hypermutation promoting antibody binding against hepatitis B virus core antigen (HBcAg) within tumor tertiary lymphoid structures (TLSs) in these type B-late recurrence patients. Mechanistically, HBcAg is exported into the extracellular space, triggering local B cell and antibody responses and complement activation. In mice, these high-affinity HBcAg-reactive antibodies lead to complement-mediated antitumor activity with enhanced anti-PD-1 efficacy. Thus, we uncover enhanced anti-virus B cell immunity within the TLS as a mechanism to anti-PD-1 in HCC.
Al-Mendalawi Mahmood Dhahir MD
Wang Zijun Z, Tenuta Mary M, Ngoc Le Han H, Halling Svensgaard Siri Nana SN et al.
Chronic infection with hepatitis B virus (HBV) is characterized by persistent expression of hepatitis B surface antigen (HBsAg), which is associated with profound immune tolerance. Although nucleos(t)ide analogue therapy effectively suppresses viral replication, it neither eliminates HBV nor reverses virus-specific immune dysfunction. Here, we report the results of two parallel first-in-human, dose-escalation studies evaluating a single infusion of mAb19-LS, a long-acting IgG1 monoclonal antibody targeting HBsAg, in individuals with chronic HBV infection receiving nucleos(t)ide analogue therapy. mAb19-LS was generally safe and well tolerated and induced a mean 11-fold increase in antigen clearance. The magnitude and duration of HBsAg suppression were dependent on both baseline antigen levels and mAb19-LS dose, with suppression maintained for more than 36 weeks in individuals receiving the highest dose. Reduction of circulating HBsAg was associated with uptake of HBsAg-IgG immune complexes by monocytes and dendritic cells and inflammatory reprogramming of these antigen-presenting cells. Notably, proliferation of both CD4 + and CD8 + T cells, as well as interferon-γ and TNF-α production in response to HBV antigens, were significantly increased 24 weeks after infusion. Together, these findings demonstrate that mAb19-LS is generally safe and effectively accelerates HBsAg clearance while activating antigen presenting cells and enhancing antiviral T cell responses.
Ionov Steven S, Connor Ruth I RI, Curtis Nicholas C NC, Shin Seungmin S et al.
People with cystic fibrosis (pwCF) are at increased risk of severe disease following respiratory viral infections including influenza and respiratory syncytial virus, and were therefore given priority for COVID-19 vaccination. Retrospective epidemiological data have revealed a lower incidence of SARS-CoV-2 infection and a reduced fatality rate among pwCF than in the general population, possibly from the stringent infection control measures and early adoption of protective behaviors. Despite several reports of adequate binding and neutralizing titers after vaccination, the molecular features of vaccine-elicited serum antibody repertoires in pwCF remain unknown. We performed high-resolution proteomic analysis of serum IgG, combined with next-generation sequencing of B cells, to quantitatively profile Spike (S)-reactive serological repertoires from nine infection-naïve pwCF after two doses of COVID-19 mRNA vaccine. We recombinantly expressed 20 IgG clonotypes from 6 pwCF as monoclonal antibodies (mAbs) and measured their binding and neutralization against vaccine-strain and variant viruses. All donors mounted strong binding and neutralizing titers to vaccine-strain virus. Ig-Seq revealed diverse serum repertoires in all vaccinees, with antibodies targeting the receptor-binding domain (RBD) comprising 64% of each circulating repertoire by abundance. Several serum IgG clonotypes identified across our cohort shared identical or similar IGHV and CDRH3 amino acid sequences with serum IgG from other pwCF or S-reactive mAbs isolated from non-CF individuals. These 'convergent' antibodies made up 14.6% of the anti-S repertoires in our cohort, reaching 24.8% in one pwCF. Convergent antibodies tended to be RBD-reactive and enriched in specific IGHV ; surprisingly, a higher abundance of convergent antibodies in serum correlated with a lower breadth of serum neutralization. All 20 mAbs bound Wuhan S with high affinity (EC 50 < 10 nM), and only RBD-reactive mAbs conferred neutralization to vaccine or variant pseudovirus. While most mAbs bound both the B.1.617.2 (Delta, 17/20) and B.1.1.529 (Omicron, 12/20) strains, convergent mAbs were less likely to bind either variant. Post-vaccine serum IgG repertoires in pwCF are dominated by RBD-focused, high-affinity antibodies and include a substantial convergent component shared with non-CF vaccinees. These findings demonstrate that pwCF mount antibody responses comparable to the general population, and a large group of convergent antibodies may contribute to strain-specific rather than cross-variant immunity.
Khodjaeva Malika E ME, Khikmatullaeva Aziza S AS, Ibadullaeva Nargiz S NS, Khudaykulova Gulnara K GK et al.
Chronic hepatitis B virus (HBV) infection is endemic in Uzbekistan. Previous data showed a high prevalence of anti-hepatitis D virus (HDV) antibodies in HBsAg-positive individuals. Limited data are available on disease severity, treatment availability and hepatocellular carcinoma (HCC) prevalence in patients with chronic HDV infection in Uzbekistan. The Scientific Research Institute of Virology (SRIoV) is the leading medical and scientific reference centre for viral hepatitis in Uzbekistan. In this retrospective study, epidemiological, clinical and laboratory data were collected and analysed from all HBsAg-positive patients presenting to the SRIoV between June 2023 and May 2024. Data from HDV-coinfected and HBV-monoinfected patients were compared. Data of 1393 individual patients were included. HDV coinfection was more prevalent than HBV-monoinfection (73.9% [n = 1030/1393]) vs. 26.1% [n = 363/1393]. HDV-infected patients were significantly younger (41.9 vs. 45.4, p < 0.001) and showed higher rates of cirrhosis (78.4% vs. 43.9%, p < 0.001) with the majority of patients being classified as Child-Pugh score B (57.8%). Only a minority of HDV-coinfected patients has ever received anti-HDV-directed treatment (0.4%, n = 4/1030). Consecutively, HDV RNA was detectable in 78.9% (812/1023) of patients. Quantitative HDV RNA was independently associated with ALT elevation > upper limit of normal. The HCC detection rate was low in both patient groups due to insufficient screening measures (HDV: n = 7/1030, HBV: n = 11/363). In this retrospective cohort of 1393 individual patients, HDV coinfection exceeds HBV monoinfection in prevalence and disease severity. Most HDV-infected patients present with advanced liver disease and currently lack access to HDV-directed therapy.
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