Paclitaxel-induced Immune Dysfunction and Activation of Transcription Factor AP-1 Facilitate Hepatitis B Virus Replication.

Background and Aims: Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment. Methods: The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice. Results: PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota. Conclusions: PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

Exploring blood lipids-immunity associations following HBV vaccination: evidence from a large cross-sectional study.

Introduction: Serological responses following hepatitis B vaccination are crucial for preventing hepatitis B (HBV). However, the potential relationship between serum lipid levels and immunity from HBV vaccination remains poorly understood. Methods: In this study, we conducted an analysis of the National Health and Nutrition Examination Survey (NHANES) data spanning from 2003 to 2016. Multivariable weighted logistic regression models, generalized linear analysis, stratified models, smooth curve fitting, segmentation effect analysis and sensitivity analysis were utilized to assess the relationships. Results: After adjusting for relevant covariates, we observed that low levels of high-density lipoprotein cholesterol (HDL) were independently linked to a significantly lower seroprotective rate. Compared to HDL levels of ≥ 60 mg/dL, the odds ratios (ORs) for individuals with borderline levels (40-59 mg/dL for men, 50-59 mg/dL for women) and low levels (< 40 mg/dL for men, < 50 mg/dL for women) were 0.83 (95% CI 0.69-0.99) and 0.65 (95% CI 0.56-0.78), respectively. This association was particularly pronounced in individuals aged 40 or older. Conversely, higher levels of the triglyceride to HDL (TG/HDL) ratio (OR, 0.90; 95% CI, 0.84-0.98), total cholesterol to HDL (Chol/HDL) ratio (OR, 0.77; 95% CI, 0.64-0.92), and low-density lipoprotein to HDL (LDL/HDL) ratio (OR, 0.85; 95% CI, 0.76-0.96) were associated with a decreased likelihood of seroprotection. Conclusion: This study suggests that lipid levels may play a role in modulating the immune response following HBV vaccination.

Real-world effectiveness of an intranasal spray A8G6 antibody cocktail in the post-exposure prophylaxis of COVID-19.

Previously, we identified an antibody combination A8G6 that showed promising efficacy in COVID-19 animal models and favorable safety profile in preclinical models as well as in a first-in-human trial. To evaluate the real-word efficacy of A8G6 neutralizing antibody nasal spray in post-exposure prophylaxis of COVID-19, an open-label, non-randomized, two-arm, blank-controlled, investigator-initiated trial was conducted in Chongqing, China (the register number: ChiCTR2200066416). High-risk healthy participants (18-65 years) within 72 h after close contact to COVID-19 patients were recruited and received a three-dose (1.4 mg/dose) A8G6 treatment daily or no treatment (blank control) for 7 consecutive days. SARS-CoV-2 infection occurred in 151/340 (44.4%) subjects in the blank control group and 12/173 (6.9%) subjects in the A8G6 treatment group. The prevention efficacy of the A8G6 treatment within 72 h exposure was calculated to be 84.4% (95% CI: 74.4-90.4%). Moreover, compared to the blank-control group, the time from the SARS-CoV-2 negative to the positive COVID-19 conversion was significantly longer in the AG86 treatment group (mean time: 3.4 days vs 2.6 days, p = 0.019). In the secondary end-point analysis, the A8G6 nasal treatment had no effects on the viral load at baseline SARS-CoV-2 RT-PCR positivity and the time of the negative COVID-19 conversion. Finally, except for 5 participants (3.1%) with general adverse effects, we did not observe any severe adverse effects related to the A8G6 treatment. In this study, the intranasal spray AG86 antibody cocktail showed potent efficacy for prevention of SARS-CoV-2 infection in close contacts of COVID-19 patients.