Viral immunology最新文献

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging zoonotic disease caused by the tick-borne SFTS virus (SFTSV), with a case fatality rate of 16.2-32.6% in East Asia. Currently, no approved vaccines or antiviral treatments exist. Monoclonal antibody (mAb) therapy offers rapid immune protection and is a promising strategy against SFTSV. This review outlines advances in SFTSV neutralizing mAb research, covering conventional generation methods (hybridoma, phage display) and innovative approaches such as single B cell sequencing. We also introduce computational tools like artificial intelligence -assisted epitope prediction and in silico mAb design. Furthermore, we discuss the structure-function relationships of mAbs targeting Gn and Gc glycoproteins, their mechanisms (e.g., fusion inhibition, receptor blockade), and key functional attributes including breadth, potency, and cross-reactivity. Challenges such as limited epitope accessibility, immune interference, and antibody-dependent enhancement are highlighted. Finally, we propose a multipronged strategy integrating structure-guided engineering, high-throughput screening, and rigorous preclinical evaluation to accelerate the development of safe and effective SFTSV therapeutics.

The hepatitis delta virus (HDV) is a defective and small, blood-borne viroid-like pathogen that coinfects with the hepatitis B virus (HBV) in about 5% of the infected individuals as it is a satellite virus of HBV. The treatment of HDV infection is quite challenging because there is no vaccine against HDV. Several commercial PCR and in-house assays have been developed, but there are greater variations in the results of these assays because they are not standardized properly. Studies are also delayed because of the unavailability of commercial HDV-specific antibodies for the diagnosis of HDV infection, even for the research devotions. To fill this gap, the recombinant antigenic HDAg protein of genotype I of HDV from the local isolate was successfully expressed and purified in the Escherichia coli (E. coli) system, followed by anti-HDAg antibodies production in rabbits. After determining and amplifying the antigenic region of HDAg of HDV, the fragment was cloned into the pET-28a vector and expressed in E. coli TOP10 cells. Following the successful expression of recombinant HDAg protein with a His-tag at its C-terminal end, we purified the HDAg protein using affinity chromatography. Both the expression and purification of HDAg-An protein were confirmed through SDS-PAGE and Western blot analysis. Through proper optimization, the HDAg-An protein was obtained with more than 90% purity. The next step involved immunizing Japanese White rabbits with the purified HDAg. The immunization protocol included 80 µg of HDAg-An in two subcutaneous priming doses and four 40 µg booster doses, followed by blood collection two weeks after each boost to monitor antibody production. The level of anti-HDAg antibodies in the rabbit serum was assessed using a quantitative ELISA technique. In the future, these antibodies could be used for the development of HDV-specific in-house assays as well as vaccines against the HDV genotype I that is locally predominant, potentially decreasing the burden of imported diagnostic tools and reagents.

Background: Interleukin-37 (IL-37) can prevent liver damage and may be an important candidate for use as a novel therapeutic tool in hepatitis B virus (HBV) infection. This study aimed to evaluate the serum levels of IL-37 in individuals with chronic HBV (CHB) infection, those who spontaneously cleared (SC) HBV infection, compared with healthy control (HC) subjects. Materials and Methods: This case-control study included 30 patients with CHB (17 males, 13 females; mean age, 50.13 ± 14.51), 30 subjects with SC HBV infection (16 males, 14 females; mean age, 51.50 ± 16.85), and 42 HC subjects (22 males, 20 females; mean age, 53.52 ± 14.44). Blood samples were collected, and then serum IL-37 levels were measured using an enzyme-linked immunosorbent assay kit. Results: Our results showed that serum IL-37 levels were significantly higher in the CHB (96.99 ± 13.39 pg/mL) than in the HC group (37.85 ± 2.99 pg/mL, p = 0.02). No statistically significant differences were found in IL-37 serum levels between CHB group and SC group (91.93 ± 17.11 pg/mL, p = 0.43). Correlation analysis showed a significant negative correlation between serum IL-37 levels and age in SC subjects (p = 0.02, R = -0.42). Conclusion: Our results suggest that increased production of IL-37 may biologically act as a negative feedback loop to attenuate the release of pro-inflammatory cytokines and subsequently alleviate disease symptoms in CHB. The negative correlation between the cytokine and age may indicate that higher levels of IL-37 in younger individuals may lead to the spontaneous clearance of HBV.

The objective of this study is to examine the general characteristics, clinical manifestations, laboratory findings, and imaging features of patients with lung adenocarcinoma who develop influenza pneumonia while undergoing immunotherapy. A retrospective analysis was conducted on the clinical data of 48 patients with lung adenocarcinoma and pulmonary infections who received immunotherapy as a stand-alone treatment between September 2022 and September 2024 at the Affiliated Hospital of North China University of Science and Technology. Clinical characteristics of patients with concurrent influenza pneumonia were assessed. When compared with the non-influenza pneumonia group, patients in the influenza pneumonia group demonstrated significantly more severe systemic symptoms, elevated urea nitrogen levels, reduced platelet counts, decreased serum albumin levels, lower Prognostic Nutritional Index values, and higher prevalence of bilateral and multilobed lung involvement. Chest imaging frequently revealed ground glass opacities, reticular patterns, and the "crazy paving" sign. Additionally, this group exhibited higher CURB-65 scores and an increased need for intensive care unit admission, with all comparisons yielding p values <0.05. Hypotension emerged as a potential factor influencing mortality in both groups (odds ratio = 9.094, p = 0.041). Among the 19 patients with lung adenocarcinoma and influenza pneumonia, 89.5% had coinfections with other pathogens. Gram-negative bacterial infections were the most common (64.7%), with Klebsiella pneumoniae subspecies, Pseudomonas aeruginosa, and Haemophilus parainfluenzae identified as the leading pathogens. Fungal infections, primarily involving Aspergillus species, accounted for 23.5% of cases. General characteristics, clinical manifestations, laboratory findings, and imaging features are essential references for the diagnosis and management of lung adenocarcinoma complicated by influenza pneumonia. Particular attention should be directed to blood pressure fluctuations, with careful monitoring of low blood pressure, especially when accompanied by bacterial infections.

Background: In a subgroup of patients, coronavirus disease (COVID)-19 is a severe illness with high mortality due to hyperinflammation, development of acute respiratory distress syndrome, and multiorgan dysfunction syndrome. Complement system activation plays a critical role in the pathogenesis and severity of COVID-19 disease. Methods: This cross-sectional, single-center study aimed to investigate the correlation between serum C3 and C4 levels and COVID-19 severity. We included 125 patients hospitalized between December 2020 and March 2021. Patients were stratified into three groups based on the level of respiratory support needed to maintain adequate oxygenation (PaO₂ ≥ 60 mmHg): 51 patients requiring oxygen supplementation up to 15 L/min, 51 patients requiring high-flow oxygen therapy, and 23 patients requiring mechanical ventilation (MV). We analyzed the blood counts and serum levels of C3, C4, C-reactive protein (CRP), IL-6, procalcitonin, d-dimers, high-sensitive troponin I (TnI), N-terminal pro-brain natriuretic peptide (NT-proBNP), IgA, IgG, IgM, C3, C4, rheumatoid factor, and anticitrullinated peptide antibodies. Results: Patients on MV had significantly lower levels of C3 and C4 (0.98 ± 0.24 g/L for C3 and 0.21 ± 013 g/L for C4) compared with patients with less severe disease (p < 0.001 for C3, p < 0.001 for C4). Serum C3 and C4 levels were lower in patients requiring high-flow oxygen therapy than in those requiring oxygen supplementation, however, the difference was not statistically significant. In addition, higher neutrophil counts were observed in patients on MV or high-flow oxygen therapy than in those on oxygen supplementation, and higher CRP, procalcitonin, and NT-proBNP levels were observed only in patients on MV. The levels of IL-6, d-dimers, and high-sensitive TnI were positively correlated with disease severity, whereas lymphocyte counts showed a negative correlation, and these differences were statistically significant among all three groups. Conclusion: The determination of serum levels of C3 and C4, along with other known laboratory risk factors, may contribute to the detection of patients at an increased risk for severe COVID-19.

To assess the dynamics of humoral immune responses to inactivated SARS-CoV-2 vaccines across populations with and without prior COVID-19 infection, a longitudinal cohort study was conducted. A total of 38 COVID-19-recovered individuals and 165 naïve participants (without prior COVID-19 infection) were enrolled, all of whom completed a two-dose vaccination regimen. Levels of anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibodies were analyzed at baseline and post-vaccination time points, including 6 weeks post-first dose, and 1 month and 6 months post-second dose. Among naïve participants, the seropositivity rate for anti-S antibodies increased to 96.23% at 1 month after the second dose with anti-S titers peaking at a median of 54.59 U/mL (p < 0.0001). Conversely, COVID-19-recovered participants exhibited significantly elevated anti-S levels after the first dose (median titer: 637.70 U/mL, p < 0.0001), with no notable changes following the second dose. Anti-S levels in both groups declined by 6 months post-second dose. The dynamic pattern of anti-N antibodies was comparable to that of anti-S, albeit with weaker vaccine-induced responses. Notably, levels of both anti-S and anti-N antibodies decreased with advancing age (p < 0.001). Males demonstrated lower anti-N antibody levels compared with females (p = 0.038), while the presence of underlying diseases was associated with higher anti-S antibody levels (p = 0.030). In conclusion, two doses effectively augmented antibody levels in naïve individuals, whereas a single dose may suffice to confer immune protection in COVID-19-recovered individuals. Antibody levels wane over time, necessitating further investigations into the durability of vaccine-mediated immune protection, evidence-based recommendations for preventive vaccination, and the formulation of immunization strategies tailored to distinct populations.

Background and aims: Chronic hepatitis B (CHB) drives liver fibrosis, contributing to chronic liver disease. Galectin-3 (Gal-3), a lectin linked to inflammation and fibrosis, was investigated for its association with liver injury severity in HBeAg-negative CHB and chronic hepatitis B virus (HBV) infection (CHI) patients. Methods: We enrolled 25 CHB, 25 CHI, and 25 healthy controls. Serum Gal-3 levels were measured in all subjects, with liver biopsies performed in CHB patients. Gal-3 and HBV DNA levels were monitored at 0, 1, 3, 6, and 12 months during antiviral therapy in CHB patients. Results: Serum Gal-3 levels were significantly higher in CHI (median: 422 U/L, interquartile range [IQR]: 144-900) and CHB (median: 567 U/L, IQR: 196-1093) patients than controls (median: 179 U/L, IQR: 79-350; p < 0.001). Although Gal-3 levels were higher in CHB than CHI, the difference was not significant (p = 0.08). Median Gal-3 levels in CHB patients decreased from 567 U/L to 288 U/L after 12 months of antiviral therapy (p = 0.043 after excluding an outlier). Gal-3 levels showed weak correlations with HBV DNA (Spearman's rho = 0.32, p = 0.12), ALT (rho = 0.28, p = 0.17), and fibrosis scores (rho = 0.35, p = 0.09). Conclusions: Elevated Gal-3 levels correlate with HBeAg-negative CHB and CHI, with a significant decline posttreatment in CHB. If validated, Gal-3 could serve as a noninvasive marker for fibrosis and treatment response.

This study aimed to generate a monoclonal antibody (mAb) against feline coronavirus (FCoV) spike (S) protein and to develop a colloidal gold immunochromatographic strip for the rapid and accurate FCoV detection. BALB/c mice were immunized with the purified protein, and hybridoma technology was employed to produce highly effective mAb. A positive hybridoma cell line (E5) was identified, which stably secreted mAb with a high titer of 1:256000 against the FCoV S recombinant protein. Western blot analysis confirmed the mAb E5's specificity. The established test strip can detect FCoV specifically and detect the antigen concentrations as low as 1.2 × 10^-7 mg/mL. The diagnostic sensitivity and specificity of the FCoV detection strip for feline coronavirus infections were 94.2% and 100%, respectively, as confirmed by reverse transcription polymerase chain reaction (RT-PCR). The detection strip demonstrated no cross-reactivity with other feline pathogens and showed consistent results in reproducibility tests. The developed colloidal gold test strip offers a highly sensitive and specific tool for rapid FCoV detection, contributing to improved real-time epidemic monitoring.

Following reports of highly pathogenic avian influenza H5N1 infections of dairy cattle in the United States in March 2024, we established a Pan-Canadian Milk network to monitor retail milk in Canada. Milk samples from across Canada that had previously tested negative for influenza A virus (IAV) RNA were tested for the presence of anti-IAV nucleoprotein (NP) antibodies as an indicator of past infection of dairy cattle. None of the 109 milk samples tested had evidence of anti-IAV NP antibodies. This is consistent with previous findings from our academic group as well as others including federal testing initiatives that have not found any IAV RNA in milk. Although not surprising given that no cases of H5N1 in cattle have been reported in Canada to date, this work further supports that the extensive outbreak in dairy cattle in the United States has not extended northward into Canada, and the integrity of the Canadian milk supply remains intact.

SARS-CoV-2 has evolved into several variants of concern, with Omicron and its subvariants currently being the most prevalent. Previously, we developed a mouse monoclonal antibody (m1E3H12 mAb) specific to the receptor binding domain of SARS-CoV-2 Omicron spike protein, and the mAb showed neutralizing activity against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB. Here, we showed that the mAb provided protection against SARS-CoV-2 Omicron infection in K18-hACE2 transgenic mice when administered intranasally. The mAb treatment reduced viral loads in both the brain and lungs. Additionally, the elevated levels of RANTES (CCL5) and MIP-3 alpha (CCL20) in the brain following SARS-CoV-2 Omicron infection showed a decreasing trend after mAb treatment. Therefore, we conclude that our mAb specific to SARS-CoV-2 Omicron spike protein has the potential to be applied as therapeutics against SARS-CoV-2 Omicron BA.1 and its subvariants BA.5, BQ.1.1, and XBB.