China National Pharmaceutical · RARB · Vaccine
hepatitis-B vaccine is a vaccine developed by China National Pharmaceutical. It is approved for therapeutic indications via injectable (others).
| Company | China National Pharmaceutical |
| Drug Class | Vaccine, Large Molecules |
| Molecular Target | RARB |
| Route | Injectable (Others) |
| Status | Approved |
hepatitis-B vaccine acts on 1 molecular target:
| RARB | retinoic acid receptor beta (RRB2, HAP) |
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.
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.
Johne Reimar R, Althof Nadine N, Maunula Leena L, Nasheri Neda N et al.
Hepatitis E virus (HEV) is the causative agent of an acute or chronic hepatitis in humans. Genotypes 3 and 4 are zoonotic and mainly infect domestic pigs, wild boars and deer. Consumption of liver and liver-containing products from these animals pose a high risk of human infection. However, the role of undercooked meat and meat products in HEV transmission is less clear. This review therefore summarizes the current knowledge on HEV detection in meat and meat products and the infection risks associated with their consumption. Detection of HEV RNA in muscles of experimentally infected pigs and in muscle meat of wild boars was repeatedly reported. The detection rate in pork products was generally lower, but up to 26% in salami-like raw sausages in one study. Detected viral genome amounts were mostly low. In spiking experiments, HEV exhibited a high stability during production and storage of raw meat products. Several case reports and case control studies point to meat and meat products as sources of HEV infection. In conclusion, several lines of evidence indicate a considerable risk of undercooked or raw meat and meat products for HEV transmission, albeit to a lower extent than liver-containing products. Standardized HEV detection methods for meat and meat products are needed to improve comparability of prevalence studies and outbreak investigations. Measures to control HEV, such as improved slaughter hygiene, avoidance of diaphragm in raw sausage production, application of virus-inactivating methods and targeted consumer recommendations, may help to reduce transmission by meat and meat products.
Nozaki Yusuke Y, Naito Satomi S, Ishii Ayana A, Tezuka Kyo K et al.
Most cell and gene therapy (CGT) products use human- or animal-derived raw materials during manufacturing. The viral safety of the final products must be ensured from the point of use of the biological raw materials. Cell therapy products, which involve living cells as the final product, are vulnerable to heat and chemicals and cannot be filtered. Therefore, it is not possible to establish a process for removing and inactivating viruses and microorganisms from these products, as is performed for biopharmaceuticals. Ensuring the viral safety of the final product requires rigorous control of the contamination risks posed by biological raw materials, which are considered more critical than those encountered in conventional biopharmaceutical manufacturing. Based on the consultation and review of CGT products by the Pharmaceuticals and Medical Devices Agency, we evaluated frequent issues and described the points to be considered regarding the quality control of biological raw materials used in the manufacturing of CGT products.
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.
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