Sinovac Biotech

Bifidobacterium species are widely used as probiotics; yet their strain-specific immunomodulatory mechanisms remain incompletely defined. In this study, we characterized the probiotic properties and immunomodulatory activities of two genetically distinct strains, B. lactis HOM2120, isolated from human milk, and B. longum HOM1190, isolated from infant feces. Genomic analyses revealed strain-specific features associated with environmental resilience and probiotic functionalities, including acid and bile tolerance, pathogen inhibition, and adhesion to intestinal epithelial cells, which were confirmed by in vitro assays. In RAW264.7 macrophages, HOM2120 preferentially enhanced phagocytosis and TNF-α production, whereas HOM1190 induced higher IL-6 secretion, reflecting distinct strain-specific immunomodulatory patterns. Transcriptomic profiling and qRT-PCR validation revealed distinct molecular signatures underlying these effects. HOM2120 preferentially activated NF-κB and STAT3 signaling pathways and induced higher Tnf expression, suggesting a bias toward cell-mediated immune responses. In contrast, HOM1190 more strongly modulated the PI3K–Akt signaling axis and upregulated Il6 and Cd80 expression, supporting enhanced antigen presentation and humoral immune–associated responses. These strain-specific immunological tendencies were further validated in mice. HOM2120 predominantly enhanced delayed-type hypersensitivity responses, indicative of cellular immunity, whereas HOM1190 more effectively increased hemolytic activity and antibody-producing cell numbers, reflecting preferential activation of humoral immunity. Collectively, these results suggest that HOM2120 and HOM1190 are functionally distinct yet synergistic probiotic candidates, supporting their potential application as functional food ingredients or therapeutic adjuncts to modulate host immunity.

Background/Objectives: Varicella is a highly contagious childhood disease that may cause severe complications in susceptible populations. The SV-1 cell line-based varicella vaccine (VarV [SV-1]) has been increasingly used in routine immunization; however, safety and reporting patterns during the transition from partial use to full Expanded Program on Immunization (EPI) implementation remain poorly characterized. This study aimed to evaluate the safety profile and reporting dynamics of VarV (SV-1) before and after its incorporation into the Expanded Program on Immunization in Jiangsu Province, China. Methods: A retrospective observational study was conducted using data from the Jiangsu Provincial Immunization Integrated Service Management Information System and the Chinese National Adverse Event Following Immunization (AEFI) Information System (CNAEFIS), including all reported AEFI following VarV (SV-1) vaccination among children under 6 years of age during 2021-2023. Temporal trends, distribution characteristics, and factors associated with AEFI reporting were assessed using descriptive analyses, negative binomial (NB) regression models, and interrupted time series (ITS) analysis. Results: A total of 1,208,500 doses of VarV (SV-1) were administered, and 634 AEFI cases were reported, corresponding to an overall reporting rate of 52.46 per 100,000 doses. Most reported events were mild, self-limiting common reactions, predominantly pyrexia and injection-site reactions. No serious adverse events were identified. Although no immediate level change was observed at EPI implementation, a significant increasing post-EPI trend was detected, consistent with enhanced surveillance sensitivity rather than a change in intrinsic vaccine safety. Abnormal reactions were rare and resolved without sequelae. Conclusions: AEFI reporting rates following VarV (SV-1) vaccination in Jiangsu Province were within expected ranges, predominantly mild and reversible. Findings support the favorable safety profile of the VarV (SV-1) in routine childhood immunization programs and provide real-world evidence to support continued implementation of the two-dose varicella vaccination strategy within the EPI.

Abstract Purpose: Germline mutations were evaluated in 530 Chinese breast cancer (BC)patients with different HER2 expression status plus 98 patients with atypical ductalhyperplasia or a breast cancer family history. Methods: DNA extracted from blood samples was analyzed with a next generationsequencing based multigene panel, with reporting of likely pathogenic and pathogenicvariants (PV) of 102 cancer associated genes, and correlation betweenclinicopathologic characteristics and known BC-associated genes. Results: The 71 identified PVs were categorized into five distinct pathway clusters:BRCA/FANC, DDR, HRR, FANC, and Other. The distribution of PVs enriched withinthese clusters differed significantly between BC patients and unaffected individuals(p=0.031). This difference was primarily driven by the BRCA/FANC, FANC, and DDRclusters, with enrichment percentages of 57.7% vs. 16.7% (BRCA/FANC), 7.0% vs.25.0% (FANC), and 15.5% vs. 41.7% (DDR) in BC vs. unaffected groups, respectively.Notably, the three BC groups stratified by HER2 expression level exhibited distinct PVdistributions. Both the HER2-low and HER2-zero BC groups showed significantlydifferent distributions compared to unaffected individuals (p=0.0132 and p=0.0081,respectively). The BRCA/FANC cluster was the predominant pathway enriched in bothHER2-low (59.6%) and HER2-zero (81.8%) groups. Furthermore, the PV distributionin the HER2-zero group was significantly different from that in the HER2-high group(p=0.0028). In contrast, the distribution in the HER2-high group resembled thatobserved in non-BC individuals. These findings indicate that BC patients with differentHER2 expression statuses harbor distinct germline PV signatures, which correlate withdifferential clinical outcomes following neoadjuvant systemic therapy. Discussion: Chinese breast cancer patients with different HER2 expression statusdemonstrated different pathogenic germline variant, which correlated with differentclinical outcome after neoadjuvant therapy. Multi-gene genetic test for pathogenicgermline variant should be offered to breast cancer patients as well as high-riskindividuals at risk for future breast cancer who would benefit from prevention and earlydetection programs. Citation Format: N. Liao, J. Wu, G. Zhang, J. Weitzel, C. Balch. Pathogenic germline variants associated with different HER2 expression among breast cancer patients [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-05-21.

ABSTRACT Leritrelvir is a groundbreaking oral antiviral for COVID‐19, distinguished as the first ritonavir‐free, covalent inhibitor targeting the SARS‐CoV‐2 3CL protease. To enable its scalable and economical manufacture, we developed a robust, multikilogram‐scale synthesis of the key chiral α‐hydroxyamide intermediate WUT‐8. Starting from commercially available methyl ( S )‐2‐(Boc‐amino)‐3‐[( S )‐2‐oxopyrrolidin‐3‐yl]propanoate (WUT‐1), an optimized four‐step sequence delivers α‐hydroxyamide intermediate ( WUT‐8 ) in 85.2% overall yield and >99% HPLC purity without a single column chromatographic purification. Key innovations include (1) a solvent‐controlled NaBH 4 reduction that preserves stereochemical integrity, (2) a one‐pot oxidation–isonitrile addition protocol to avoid the isolation of a sensitive aldehyde intermediate, and (3) a recrystallization‐based purification (ethyl acetate/ n ‐heptane) that replaces column chromatography. The process has been successfully scaled to produce WUT‐8 in 82.5 kg batches under cGMP‐ready conditions, demonstrating excellent stability and reproducibility. This work establishes a practical, high‐yielding, and column chromatography‐free route to WUT‐8, providing a reliable industrial supply for the production of leritrelvir.

BackgroundOptical genome mapping (OGM) is an emerging cytogenetic method for concurrently detecting structural variants (SVs) and copy number variants (CNVs). However, its clinical application in prenatal diagnosis remains underexplored.MethodsThis study retrospectively evaluated the clinical validity of OGM in prenatal diagnosis by comparing with two routine genetic testing methods: karyotyping and chromosomal microarray analysis (CMA). Both positive and negative cases detected by routine genetic methods were enrolled to evaluate the technical concordance of OGM and its capability to improve diagnostic rate in negative cases. The exclusion criteria were balanced centromeric translocations, mosaic cases with cellular fractions < 20%, and loss of heterozygosity (LOH) < 25 Mb. All samples subjected to OGM testing were anonymized and analyzed blindly. The results from OGM were compared with those from routine genetic testing, and statistical analyses were performed to assess technical concordance and diagnostic rate.ResultsOf 217 samples (166 positive samples and 51 negative samples for routine genetic testing), all were successfully tested with OGM, including 2 umbilical cord blood samples, 4 chorionic villi samples, and 211 cultured amniotic fluid samples. Of the 207 reportable chromosomal aberrations from 166 positive samples, the blinded concordance between OGM and CMA, karyotyping, and combination of karyotyping plus CMA was 97.81%, 96.36%, and 97.10%, respectively. OGM missed six aberrations initially, including one LOH, two marker chromosomes, and three microdeletions. However, after reanalysis, its concordance improved to 100% with CMA and 99.03% with karyotyping plus CMA. OGM also diagnosed one additional case of a 3-kb deletion in 51 negative samples, improving the diagnostic rate by 1.96%. Moreover, OGM reclassified the pathogenicity of two microdeletions from pathogenic to uncertain significance in 2 positive cases. Furthermore, OGM clarified the diagnosis suspected by routine genetic testing and improved diagnostic accuracy in some cases.ConclusionAs far as we know, this is the largest retrospective study on OGM in prenatal diagnosis, and it includes a broad range of sample types. The results showed that OGM exhibits high concordance among the tested methods and increases the diagnostic rate. Thus, OGM has the potential to become a first-line technique for prenatal diagnosis in the future.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12967-025-06901-9.

PurposeHIV drug resistance is increasing globally, especially in resource-limited settings. NNRTIs, commonly used as first-line ART, have a low genetic barrier and are prone to resistance mutations. Lifelong ART contributes to the accumulation of drug resistance mutations (DRMs), compromising treatment efficacy. Genotypic resistance testing is essential before initiating or modifying ART. However, the Sanger sequencing method relies on successful PCR amplification, which is often suboptimal in low viral load (VL) samples, limiting sensitivity and coverage.Patients and MethodsWe developed an optimized primer system targeting conserved regions in the protease (PR), reverse transcriptase (RT), and integrase (IN) genes, covering PR aa 1–99, RT aa 1–410 (including NNRTI resistance sites Y318 and N348), and IN aa 1–288. A total of 2,071 HIV-positive plasma samples collected in China (Jan 2023–Dec 2024) were analyzed using a PCR-Sanger sequencing method. Subtyping was performed using BLAST, COMET 2.4, and the HIV-1 Gene Sequences Database (China). Amplification success rates and mutation detection were evaluated across VL levels.ResultsThe overall amplification success rates were 87.40% (1,810/2,071) for the PR/RT region and 87.06% (1,803/2,071) for the IN region. In samples with VLs of 50–200 copies/mL, the success rates remained above 80% for PR/RT and 78.10% for IN. For samples with VL ≥1000 copies/mL, both regions achieved amplification rates above 99%. Among eight samples harboring Y318 or N348 mutations, all were successfully amplified at 1000, 400, 200, and 100 copies/mL. Three of them consistently yielded detectable mutations across all gradients. Subtyping revealed CRF01_AE and CRF07_BC as the predominant strains, consistent with national epidemiological trends.ConclusionThe optimized system improves amplification sensitivity and mutation coverage, especially in low-VL samples. It enables stable detection of key NNRTI resistance mutations and shows strong subtype compatibility, supporting its utility in clinical resistance surveillance and early detection.

Significant physiological changes occur in both the fetus and the mother during pregnancy. Urine proteins have been shown to reflect a wide range of physiological and pathological changes in the body. This study employed low-abundance protein-enriched magnetic nanobeads to conduct an in-depth analysis of the daily changes in urine proteins throughout the entire pregnancy of rats. Based on the 3455 identified urine proteins, fetal and maternal dynamic changes were observed in the pregnancy group compared to the control group, including blastocyst formation and cell division in the early stage of pregnancy. In addition, the morphogenesis- and development-related organs and tissues are significantly enriched at different stages of pregnancy. The 9th day after pregnancy is the stage when organ development is most concentrated, especially the nervous system and vasculature development. During the late stage of pregnancy, maternal-specific changes were observed, such as lactation. These results indicate that urine protein can reflect the fetal and maternal dynamic physiological alterations during pregnancy, which suggests the potential value of urine protein analysis in pregnancy health monitoring. It is emphasized that the analysis focuses on the daily variations in the urine proteins, as these daily changes are expected to reveal more dynamic and detailed information about the physiological processes during pregnancy.