The diversity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine platforms and widespread natural exposure have created a complex landscape of humoral immunity requiring detailed characterization. Here, we compare nucleocapsid (N)- and spike (S)-specific antibody responses in sera from infected humans (IH) during the first pandemic wave (April-August 2020) and in vaccine recipients (Sinopharm, Sinovac, or AstraZeneca) using commercial ELISA kits. Among naturally IH, the IgG-positivity rate was higher for N (80.9%) than S (42.8%), with significantly elevated N-specific IgG levels compared to prepandemic controls (p-value <0.05), while IgM responses showed no significant differences. Strong positive correlations were observed between S- and N-specific antibody responses, particularly for IgG and its subclasses. Vaccinated cohorts exhibited high IgG positivity rate (83-100%) against both antigens with low IgM levels, and overall IgG and subclass responses were significantly elevated relative to pre-pandemic controls (p-value <0.05), with consistently strong inter-antigen correlations across groups. Overall, natural infection induces a coordinated humoral response biased toward the nucleocapsid antigen, supporting its utility as a marker of recent infection, whereas vaccination elicits a robust multi-subclass antibody response with platform-dependent differences in antigen recognition and subclass distribution.
It is widely known that numerous enveloped viruses can produce multinucleated cells (syncytia) as a result of viral entry-related membrane fusion events. By protecting the virus from the host's immune reaction, these syncytia are thought to promote viral reproduction. Syncytia are collections of merged cells. A viral spike protein (S) on the surface of an infected cell interacts with receptors on nearby cells to cause the syncytia response. The innate immune system's response to viruses affects how syncytia form. Some interferon-stimulated genes change the membrane in a way that reduces the likelihood of fusion. The severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus is quickly changing; also, several mutations occurred in its S protein. Individually and together, the Alpha, Beta, Gamma, and Delta variants carry mutations that significantly affect S function and syncytia formation. The function of syncytia in newly emerging variant diseases is still unknown, though. Syncytia could cause disease through promoting viral transmission, cytopathicity, immunological evasion, and inflammatory responses. The SARS-CoV-2 S protein variations include several changes that improve receptor interactions, fusogenicity, and antibody reactivity. A wide range of clinical symptoms, including moderate febrile sickness, severe respiratory distress, and occasionally deadly lung damage, can be brought on by an infection with SARS-CoV-2. Several of these lung illnesses (MERS-CoV) are linked to both the Middle East Respiratory Syndrome (MERS) and the severe acute respiratory syndrome coronavirus (SARS-CoV). Compared to acute respiratory syndromes, the lung thrombosis brought on by Coronavirus disease 2019 (COVID-19) is incredibly severe. In this review we focused on innate immunological elements that prevent syncytia from forming and the molecular triggers of S-mediated fusion.
Mammalian reoviruses are promising oncolytic agents, but most preclinical and clinical work has focused on the type 3 Dearing (T3D) prototype, potentially underestimating the therapeutic relevance of broader reovirus genetic diversity. Because reoviruses possess a segmented double-stranded RNA genome, reassortment can generate progeny with novel combinations of traits influencing infectivity, replication, and cytotoxicity. Here, we evaluated a panel of previously generated T1L × T3D reassortants and recombinant reoviruses across three epithelial tumor models: A549 lung adenocarcinoma and the oral squamous carcinoma cell lines OECM-1 and CAL-27. Across all three models, the tested viruses displayed marked cell line-dependent heterogeneity in both cytotoxicity and infectivity. Several reassortants reduced viability more effectively than the parental T1L and T3D strains in one or more cell lines, and DB62 emerged as the most broadly active candidate across the panel. Infectivity and cytotoxicity overlapped only partially, indicating that efficient infection alone does not fully predict oncolytic potency. Together, these findings show that reassortment can generate reoviruses with enhanced or selective activity across epithelial tumor contexts and support future studies examining how segment-dependent differences in interferon antagonism, entry, and cell death shape oncolytic potency.
Background:The ongoing spillover of highly pathogenic avian influenza H5N1 virus into mammalian species, including recent outbreaks in dairy cattle, underscores an urgent need for broadly effective therapeutics. Nanobody, the variable domain of heavy chain-only antibody, offers unique advantages for viral neutralization due to its small size, stability, and accessibility to cryptic epitopes.Methods:In this study, we isolated a human nanobody, nAb35, targeting the hemagglutinin of the dairy cattle H5N1 virus A/Texas/37/2024 (clade 2.3.4.4b) via phage display of a human nanobody library. After three rounds of panning against the recombinant H5 ectodomain, a dominant clone (nAb35) was highly enriched. Then nAb35 was fused with a human IgG1 Fc fragment and expressed as a bivalent dimer.Results:Biochemical characterization demonstrated that nAb35 specifically binds to H5 under both denaturing and native conditions and recognizes a linear epitope accessible on H5 expressed on the cell surface. In vitro neutralization assays using H5 pseudovirus showed that nAb35 inhibited viral entry with a half-maximal effective concentration of approximately 10 μg/mL, as determined by both luciferase reporter and immunofluorescence assays.Conclusion:These findings identify nAb35 as a promising candidate for further therapeutic development against emerging H5N1 virus.
Rustrela virus (Rubivirus strelense) is a single-stranded, non-segmented RNA virus that causes brain diseases in animals, especially encephalitis and meningoencephalitis. Its rapidly mutating RNA genome complicates control, making a vaccine imperative. Immunoinformatics approaches were employed to make the polyepitope vaccine (PEV) for RuV control. Epitopes for cytotoxic T lymphocytes (CTL), helper T lymphocytes (HTL), and B cells were made from most immunogenic parts i.e., E1, E2, and capsid structural proteins of RuV. Epitopes that were antigenic, not allergic, IFN simulators, and not toxic were selected. This led to the selection of 6 CTL, 6 HTL, and 13 B cell epitopes, which were then used to construct the PEV with appropriate linkers and CTB as an adjuvant for immunological modulation. The physiochemical analyses demonstrated that the PEV was safe, stable, hydrophilic, and soluble. The secondary structure prediction has indicated mostly coiled and alpha helix in the PEV. The 3D scans revealed a solid and stable structure. The interactions and stability between the vaccine, TLR3, TLR4, and TLR7 were revealed by molecular docking. The vaccine candidate's minimal deformability and high stability were verified by molecular dynamics modeling. The developed PEV vaccine demonstrated a strong immunological response in in silico immune simulation. RuV-PEV is predicted to be efficiently produced in E. coli following in silico codon optimization and vector cloning. It elicited strong antigen-specific humoral and cellular responses, indicating promise as a Rustrela virus vaccine. Its precise effectiveness, safety, and immunogenicity profile may be confirmed by further experimental validations.
This study aimed to explore the molecular alterations in airway epithelial cells in children with wheezing infected by respiratory syncytial virus (WheezeRSV). This study extracted the single-cell sequencing data of two control and wheezeRSV samples from GSE286262 dataset. The monocle2 was performed for analyzing evolution process of basal cells along disease progression. Kyoto encyclopedia of genes and genomes and gene ontology were carried out to identify the function enrichment of differentially expressed genes (DEGs) between WheezeRSV and control groups. Additionally, human nasal epithelial cells (HNECs) were harvested, and quantitative real-time polymerase chain reaction (qRT-PCR) was applied to detect the expression levels of key genes. Six cell types including ciliated cells, KRT5 + basal cells, TP63 + basal cells, KRT80 + epithelial cells, goblet cells, and club cells. The differentiation trajectory analysis on basal cells indicated two distinct branches including ciliary assembly and keratinization. Then, function analysis indicated that ciliated cells were involved in leukocyte transendothelial migration, cellular senescence and angiogenesis. Goblet cells were associated with IL-17 signaling pathway, apoptosis, and ferroptosis, and club cells were enriched in the apoptotic process and innate immune response. The qRT-PCR results revealed that the mRNA expression levels of TEKT2 , SPRR3 , ITGB1 , CDKN1A , ACSL1 , and CXCL8 were markedly upregulated in the WheezeRSV group ( p < 0.01). Basal cells differentiated into keratinocytes and ciliated cells as the disease progresses, thereby enhancing defense and repairing the epithelial barrier. Meanwhile, wheezeRSV enhanced the activity of apoptosis and inflammatory response of ciliated cells, goblet cells, and club cells.
The hyperinflammatory response in COVID-19 is a major factor contributing to morbidity. Pentoxifylline, a methylxanthine derivative, has immunomodulatory properties, but its effects on inflammatory markers in COVID-19 remain unclear. This meta-analysis aims to evaluate the efficacy of pentoxifylline supplementation on CRP and interleukin-6 (IL-6) levels in these patients. A systematic search was conducted across multiple databases for randomized controlled trials (RCTs) published up to September 2025. Four RCTs, including 178 cases and 321 controls for CRP, and two RCTs, including 70 cases and 70 controls for IL-6, were included. Two reviewers independently performed data extraction and assessed the risk of bias using the Cochrane tool. Pooled standardized mean differences (SMDs) were calculated using a random-effects model. Heterogeneity was analyzed through meta-regression, and the conclusiveness of the evidence was evaluated using Trial Sequential Analysis (TSA). Pentoxifylline did not significantly reduce C-reactive protein (CRP) levels compared to the control group (SMD = -0.89; 95% CI: -1.85 to 0.07; p = 0.07). However, substantial heterogeneity was noted across the studies (I2 = 95.3%). Similarly, a nonsignificant trend toward reduction was observed for IL-6 (SMD = -0.22; 95% CI: -0.96 to 0.52; p = 0.55), accompanied by significant heterogeneity (I2 = 79.1%). Given the limited number of studies included, the results are inherently fragile, and one additional trial could substantially shift the pooled estimate. Meta-regression analysis indicated that patient age and publication year did not account for the heterogeneity, although there was a nonsignificant trend suggesting that a longer treatment duration might be associated with greater CRP reduction. TSA for CRP showed that cumulative evidence suggested futility and a lack of meaningful effect, confirming a significant lack of effect. The included studies generally had a low risk of attrition and reporting bias. Current evidence does not support the use of pentoxifylline for significantly reducing CRP or IL-6 levels in COVID-19 patients. The findings regarding CRP are considered conclusive, but the limited number of studies suggests that further trials on this outcome may alter this conclusion.
In the intricate world of aquatic ecosystems, infectious pancreatic necrosis virus (IPNV) and viral hemorrhagic septicemia virus (VHSV) emerge as formidable threats to marine life, posing diverse diseases that reverberate through shared host species (Salmon, trout fishes). The coexistence of these viruses amplifies health risks, compelling the pursuit of inventive intervention strategies. Recognizing the urgency, a current and optimistic initiative strives to craft a revolutionary combined vaccine, offering protection against both IPNV and VHSV. This innovative endeavor, driven by an immunoinformatics approach, identifies immune-dominant epitopes from CadB and LamB proteins, ensuring the final vaccine's immunogenicity, non-allergenicity, and enhanced solubility. Molecular dynamics simulations validate its binding stability and structural integrity. In a pivotal move, codon optimization using Escherichia coli K12 as a model result in an ideal guanine-cytosine content and a higher Codon Adaptation Index value, seamlessly integrating into the cloning vector pET2+ (a). In essence, our outcomes underscore the potential of this proposed peptide vaccine to elicit a robust immune response against both IHNV and VHSV, marking a breakthrough in the holistic management of infectious diseases in aquatic environments.
The potential role of bovine leukemia virus (BLV), a zoonotic deltaretrovirus, in human breast carcinogenesis remains controversial, and evidence from seroepidemiological studies is limited. This study aimed to evaluate BLV IgG seroprevalence in women with malignant breast cancer and benign breast lesions and to explore the possible association between BLV exposure and breast cancer development. In this cross-sectional comparative study, a total of 124 women aged ≥18 years who presented to Ankara Etlik City Hospital between May and July 2024 were included. The malignant group comprised 82 women with histopathologically confirmed breast cancer, while the control group included 42 women with benign breast lesions. Serum samples were analyzed for BLV-specific IgG antibodies using a commercial enzyme-linked immunosorbent assay kit. Overall BLV IgG seroprevalence was 12.9% (16/124), with rates of 13.4% in the malignant group and 11.9% in the benign group, showing no statistically significant difference (p = 0.812). In the malignant group, BLV IgG seropositive patients were significantly older than seronegative patients, and seropositivity increased with age (p < 0.01). Although higher BLV IgG seropositivity were observed in invasive mucinous carcinoma cases, this association did not reach statistical significance in logistic regression analysis. Hematological parameters were evaluated to investigate potential systemic immune or inflammatory responses associated with BLV exposure; however, no significant associations were identified between BLV IgG seropositivity and these parameters. These findings suggest that BLV exposure, as reflected by humoral immune response, is not directly associated with breast cancer development but may represent cumulative or long-term exposure. Further large-scale, multicenter studies integrating molecular and serological approaches are warranted to clarify the potential role of BLV in human breast cancer etiology.
Maternal antibodies protect mink kits early in life, but their duration and impact on subsequent SARS-CoV-2 exposure remain unclear. We longitudinally characterized passive immunity in kits born to mothers previously infected with lineage B.1.1.305 on a commercial farm in Greece and related antibody kinetics to a later heterologous virus incursion. Breeder animals showed a 93.3% seropositivity rate after the initial outbreak. On day 20 postpartum, 81.4% of mothers and 69.8% of kits were positive for SARS-CoV-2 nucleocapsid (N)-specific antibodies by enzyme-linked immunosorbent assay (ELISA); a maternal S/P% >160.1% was associated with kit seropositivity at the same time-point (area under the curve 0.985; sensitivity 90%; specificity 100%). Kit seropositivity declined to 2.4% by D*56, consistent with the rapid waning of maternally derived antibodies. On D*87, 97.6% of kits had seroconverted, and 90.0% of mothers were seropositive; Analysis of oropharyngeal swabs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and next generation sequencing (NGS) confirmed introduction of lineage B.1.177. No clinical signs or excess mortality were observed during this reinfection event. These data demonstrate efficient passive transfer, rapid loss of detectable antibodies by ∼8 weeks, and farm-wide seroconversion after re-exposure to a new lineage. The absence of disease despite widespread seroconversion suggests maternally acquired immunity may have mitigated illness but did not prevent infection. Silent SARS-CoV-2 circulation can therefore occur in partially immune mink farms, with important implications for biosecurity and targeted SARS-CoV-2 surveillance. To our knowledge, this is the first longitudinal study to track the dynamics of maternally derived SARS-CoV-2 antibodies in mink kits and link them to subsequent exposure outcomes.
The SEN virus (SENV), a DNA virus that has been linked to blood transfusion, is a major cause of post-transfusion hepatitis. SENV-D and SENV-H are non-A to E hepatitis viruses. The present study was conducted to investigate the prevalence of SENV-D/H among dialysis patients and blood donors as control group in Diyala province/Iraq. This study includes 120 participants: 80 dialysis patients who have been attending the Ibn-Sina Dialysis Center-Diyala Directorate of Health were previously diagnosed with the disease, and 40 individuals as controls were selected at random from blood donors at the Central Blood Bank during the period from 1/5/2025 to 30/11/2025. Full information had been taken directly from the patients, and the information had been arranged in an informative formula sheet, which includes age and gender. All study subjects were screened for nested polymerase chain reaction. The SENV-D prevalence was 10 (12.50%) and 0.00% for dialysis patients and controls, respectively, and SENV-H was 5 (6.25%) and 1 (2.50%) for dialysis patients and controls, respectively. The SENV co-infection rate of genotypes D and H was 3 (7.50%) in the dialysis group, and no cases in the control group were found. A very strong association was found between the distinct SENV genotypes and Hepatitis B virus (HBV) or Hepatitis C virus (HCV) status. Positivity for SENV was also correlated with high serum Aspartate Aminotransferase (AST) and Alanine aminotransferase (ALT). SENV-D and SENV-H were more prevalent among hemodialysis patients than in normal blood donors. The presence of SEN-V in both groups indicates its categorization as a blood-borne virus and suggests risk for transmission by blood exposure.
The pathophysiology of multiple sclerosis (MS) bears notable similarities to the dysregulated inflammatory response occurring during coronavirus disease 2019 (COVID-19) infection. B cells play a pivotal role among immune cells in the pathogenesis of both these diseases. Consequently, clarifying the molecular mechanism underlying B cell function in COVID-19 and MS is of great significance for formulating more efficient treatment strategies. A comprehensive analysis integrating single-cell RNA sequencing (scRNA-seq), genome-wide association study, and expression quantitative trait locus data from patients with COVID-19 and MS was performed. Gene set enrichment analysis revealed pathways and functional roles associated with the key genes, while pseudotime analysis tracked their expression patterns across different B cell developmental trajectories. The results of scRNA-seq analysis showed that, in comparison with the healthy control group, the proportion of B cells rose in patients with COVID-19 and those with MS. Through differential expression analysis and Mendelian randomization analysis, DR1, IKZF3, and RUVBL2 were identified as risk factors for both COVID-19 and MS, whereas ANAPC5 was characterized as a protective factor against these two conditions. The findings of the pseudotime analysis indicated that only IKZF3 had differential expression across different branches of B cells. IKZF3's role in promoting immune inflammation and inhibiting metabolism could potentially be linked to the onset and comorbidity of COVID-19 and MS. This emphasizes not only the possible interaction mechanisms between these two diseases but also their clinical significance.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in approximately 778 million reported cases and over 7 million deaths worldwide as of August 2025 (WHO COVID-19 Dashboard), predominantly due to variable acute and chronic lung infections accompanied by inflammatory responses within the pulmonary tract and vasculature. Despite ongoing research, no definitive cure has been identified. Preventive measures, including vaccines and monoclonal antibody-based interventions, have been developed to protect vulnerable populations, and hundreds of therapeutic candidates have been evaluated worldwide. Complementing these strategies, vitamin D and zinc (Zn) supplementation have emerged as promising, accessible adjunctive strategies due to their immunomodulatory and anti-inflammatory properties. This review synthesizes current experimental, clinical, and epidemiological evidence on the roles of vitamin D and Zn in modulating immune responses relevant to SARS-CoV-2 infection. Available data suggest that adequate vitamin D and Zn status may support immune function, reduce excessive inflammation, and potentially mitigate disease severity, particularly in deficient individuals. However, clinical trial outcomes remain heterogeneous. Overall, vitamin D and Zn supplementation may be considered supportive, adjunctive preventive measures. Further well-designed randomized controlled trials are required to define their optimal use in COVID-19 prevention and management.
Noroviruses are single-stranded positive-polarity RNA viruses classified in the family Caliciviridae. Human noroviruses (HuNoVs) are a leading cause of acute viral gastroenteritis worldwide. Despite their ability to infect various epithelial and nonepithelial cell types, establishing robust in vitro culture systems for HuNoVs remains challenging. As a result, murine norovirus 1 (MNV-1) has become a widely used model for investigating norovirus biology and pathogenesis, due to its ability to replicate efficiently in primary dendritic cells and macrophages. Although different B-cell lines are susceptible to MNV-1 infection, the susceptibility of primary B lymphocytes has been poorly characterized. Here, we demonstrate that MNV-1 infects primary B lymphocytes, with infection levels increased by prior stimulation with lipopolysaccharide and interleukin-4. The enhanced infection does not appear to result from increased virion binding but instead to an increased cellular permissiveness. These findings provide new insights into the cellular tropism of MNV-1 and suggest that the activation status of B-cell influences their susceptibility to infection. This model may improve our understanding of norovirus-host-cell interactions in adaptive immune cells and could aid in the development of more representative in vitro systems for studying norovirus pathogenesis.
The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to influence the global coronavirus 2019 (COVID-19) pandemic. Even vaccinated individuals or those with prior infections may experience reinfection, depending on the immune evasion capacity of the circulating variants. Therefore, analyses of variant characteristics and immune escape are critical for informing public health policy. However, as COVID-19 has been downgraded in terms of infectious disease classification, the availability of patient sera has become increasingly limited, restricting the timely immunological analyses of emerging variants. To address this challenge, we established an antiserum production and neutralization assay system using a hamster model and demonstrated the utility of this animal serum-based approach. In this study, antisera against 10 circulating SARS-CoV-2 variants were generated in golden Syrian hamsters, and they showed high titer of humoral and neutralizing antibody using enzyme-linked immunosorbent assay and plaque reduction neutralization test (PRNT) assay. In addition, we compared serum from an unvaccinated patient (n = 1) infected with the BA.5 variant with serum from a BA.5-infected hamster (n = 1). Although the number of comparable samples was limited, the PRNT50 titer patterns in serum from an unvaccinated individual infected with BA.5 and in hamster antisera were similar. These findings indicate that antisera generated in the hamster model can provide timely immunogenicity assessments of newly emerging SARS-CoV-2 variants, thereby contributing to the rapid characterization of variant immune escape and the generation of essential data for future public health preparedness.
This study aimed to characterize Epstein-Barr virus (EBV) serological markers and EBV DNA profiles in a healthy examination cohort from Chongqing, China, and to examine their associations with routine hematological and biochemical parameters. This retrospective cross-sectional study included adults undergoing routine health examinations in Chongqing between 2019 and 2024. EBV serology (EA-IgA and VCA-IgA) was assessed in 4,535 individuals using ELISA, and EBV DNA was measured in 6,508 individuals by quantitative PCR. Hematological indices and liver and renal function markers were compared across EBV antibody subgroups and EBV DNA status. Multivariable linear regression analyses were performed with adjustment for age and sex. VCA-IgA seroprevalence was significantly higher than EA-IgA (13.38% vs. 6.09%, p < 0.001), with both peaking in the 41-50-year age group. EBV DNA was detected in 7.24% of individuals, with positivity increasing with age (≥61 years: 12.09%) and being higher in males than females (7.81% vs. 6.06%, p = 0.010). Among EBV DNA-positive individuals, 86.17% had low viral loads (<104 copies/mL). After adjustment, EBV seropositivity and EBV DNA positivity were independently associated with statistically significant differences in leukocyte subsets and hepatic and renal markers; however, all median values remained within established clinical reference ranges. EBV infection markers in this inland Chinese health examination population exhibited distinct age- and sex-related distributions and showed independent associations with subtle physiological variations rather than overt pathology. Importantly, EBV serological markers and EBV DNA demonstrated differential association patterns, indicating that they convey complementary and nonredundant biological information in assessing EBV infection status.
BK polyomavirus (BKPyV) is highly prevalent and clinically relevant in immunocompromised populations, underscoring the need for reliable serological tools to support epidemiological monitoring and clinical follow-up. This study aimed to generate a recombinant VP1-based enzyme-linked immunosorbent assay (ELISA) using a baculovirus-Sf9 insect cell system and to explore its application in a human serum cohort. Recombinant VP1 was produced by baculovirus-mediated expression, purified by nickel-nitrilotriacetic acid affinity chromatography, and used to establish an indirect IgG ELISA. A plasmid-based transient expression approach in Sf9 cells was evaluated only as a feasibility experiment and did not yield sufficient VP1 for assay development. Analytical performance was assessed using a polymerase chain reaction (PCR)-defined serum panel (n = 30), and the assay was subsequently applied to 149 sera with unknown BKPyV status. Baculovirus-mediated expression generated high-purity VP1 with an average yield of approximately 1.55 mg/mL from a 10 mL culture. PCR-confirmed positive sera showed markedly higher optical density values than PCR-negative sera, with very good analytical discrimination in this small validation set (area under the curve = 0.996). In the cohort analysis, overall seroreactivity was 89.7%, antibody reactivity increased with age, and higher ELISA signals were observed in renal transplant and hemodialysis patients than in healthy individuals. Detectable reactivity in young children may reflect early exposure or passive maternal antibodies. These findings indicate that insect cell-derived BKPyV VP1 is a suitable antigen for serological assays and a practical platform for preliminary seroepidemiological applications, which require confirmation in larger independent validation cohorts.
BACKGROUND:The emergence of highly pathogenic avian influenza A (H5N1) clade 2.3.4.4b in dairy cattle and human cases raises urgent pandemic concerns. A critical question is whether seasonal influenza vaccines elicit cross-reactive immunity against this novel zoonotic strain, potentially contributing to pre-existing population immunity. METHODS:We combined structural bioinformatics and serological analysis. Hemagglutinin (HA) protein sequence and structural conservation were assessed between World Health Organization WHO-recommended 2024-2025 vaccine strains (H1N1 A/Victoria/4897/2022, H3N2 A/Thailand/8/2022) and bovine H5N1 (A/Texas/37/2024). Cross-reactive antibodies were measured in serum from 46 vaccinated individuals using ELISA against A/Texas/37/2024 HA. Endpoint titers were the highest reciprocal dilution with absorbance >2.1-fold background. Statistical analyses included Pearson correlation (age, dose, time) and Wilcoxon rank-sum/Chi-squared tests (group comparisons). RESULTS:Structural analysis revealed 79.3% amino acid identity in the HA2 subunit between H1N1 and H5N1, with conserved epitopes in the stalk domain. Serologically, 41.3% (19/46) of vaccinated individuals had cross-reactive HA-binding antibodies with titers ≥1,280. No significant associations were found with sex, vaccine type, brand, or number of doses. A significant positive correlation existed between age and antibody titer (Pearson's R = 0.51, p < 0.001); individuals over 60 years had higher titers than younger groups. CONCLUSIONS:Seasonal influenza vaccination is associated with cross-reactive HA-binding antibodies against bovine H5N1 clade 2.3.4.4b in a substantial proportion of individuals, with responses increasing with age. This suggests pre-existing immunity from vaccination or prior exposures may influence responses to this zoonotic threat. However, the functional neutralizing capacity and protective efficacy of these antibodies are unproven. These findings highlight the potential immunological footprint of current vaccines against emerging strains and support further investigation into cross-protection. They also reinforce the importance of conserved HA epitopes as targets for next-generation universal influenza vaccines.
Vaccination is an effective way to prevent influenza virus infection. Currently, intramuscular vaccines are the most commonly used and can provide strong humoral immunity, but they may not induce the mucosal immune response well. A variety of pathogens gain access to the host via the respiratory tract, and the mucosa serves as the initial line of defense against bacterial invasions. Therefore, developing mucosal vaccines is a valuable strategy for preventing respiratory infectious diseases. The mucosal barrier hinders antigen delivery and immune activation, making efficient mucosal adjuvants crucial for vaccine advancement, though their use faces several obstacles. The main challenges faced by mucosal adjuvants are mucosal tolerance, delivery efficiency, and immune response balance. Future mucosal adjuvants will continue to focus on multitarget synergistic design and combination adjuvant application. The safety and efficacy of future influenza vaccines are contingent upon the judicious selection of suitable mucosal adjuvants. The creation of next-generation influenza vaccines will be made easier as our knowledge of adjuvants grows. In this review, we summarize the current progress and applications of mucosal adjuvants for influenza vaccines, with implications for the development of novel influenza vaccines and vaccines against other infectious diseases.
BACKGROUND:Hepatitis C is a chronic liver disease caused by infection with the hepatitis C virus (HCV), representing a major concern for global public health. The interferon gamma and interferon gamma receptor-1 (IFN-γR1) genes play a significant role in viral infections. This study aims to investigate the association between polymorphisms in the IFN-γ and IFN-γR1 genes and the chronicity of HCV infection. METHODOLOGY:This study included 310 participants, comprising 150 chronic Hepatitis C (CHC) patients and 160 healthy controls. Nucleic acids were isolated, and PCR was used for HCV detection. The intron-1 of IFN-γ and promoter-56 of IFN-γR1 genes were amplified through PCR and sequenced through Sanger's method. RESULTS:The frequency of TT, AT, and AA genotypes of the IFN-γ at +874 in CHC patients was (20%), (57%), and (23%), while in healthy control, it was (46%), (38%), and (16%), respectively (p < 0.0001). In non-cirrhotic patients, they were (25.6%), (41.1%), and (33.3%); in cirrhotic patients, they were (26.3%), (39.5%), and (34.2%), while in HCC patients, they were (18.2%), (50%), and (31.8%). The AA genotype shows significant association with chronic liver complications (p = 0.017). The frequency of TT, TC, and CC genotypes of the IFN-γR1 gene at -56 was (21%), (43%), and (36%) in CHC patients, while in healthy individuals (38%), (21%), and (41%), (p < 0.0001). In non-cirrhotic patients, they were (30%), (49%), and (21%); in cirrhotic patients, they were (32%), (44%), and (24%), while in HCC patients, they were (22%), (46%), and (32%) (p = 0.027). The TC genotype is significantly associated with an increased risk of developing liver cirrhosis and HCC in CHC patients compared to healthy controls. CONCLUSION:The current study shows that the AA genotype of the IFN-γ and TC genotype of the IFN-γR1 genes are associated with increased susceptibility and HCV chronicity. While the TT genotype of the IFN-γ and the CC genotype of the IFN-γR1 may confer a protective effect.
