PUBLICATIONS

The recent mpox outbreaks in non-endemic countries highlight the urgent need for improved therapeutics and diagnostics. In this study, monoclonal antibodies (mAbs) targeting the mpox enveloped virion antigens A35 and B6 were transiently expressed in Nicotiana benthamiana using a geminiviral vector system. Following agroinfiltration, anti-A35 and anti-B6 mAbs accumulated to 27 µg/g fresh weight at 3 days and 260 µg/g at 7 days post-infiltration, respectively. SDS-PAGE and Western blot analyses confirmed the assembly of antibodies, and the purified antibodies bound to mpox-infected Vero cells. The neutralization assays demonstrated moderate reductions in viral infection under the tested conditions. Additionally, an electrochemical immunosensor demonstrated the ability of plant-produced antibodies to detect mpox virus through antigen-antibody binding induced current changes. These results support that the plant-based systems as rapid platforms for producing mpox-specific antibodies for diagnostics and antiviral research.

BACKGROUND: Taiwan, a region traditionally considered non-endemic for dengue, experienced an unexpected and large-scale outbreak in 2023. We investigated the multifactorial drivers of this outbreak, including cross-border viral importation, serotype cocirculation, vector ecology, and climate variability.

METHODS: We analyzed national dengue surveillance data (2013-2023), meteorological records, and Breteau Index (BI) values, alongside molecular serotyping and whole-genome sequencing of clinical isolates. Time-lagged Poisson regression was used to identify predictors of indigenous dengue transmission in Kaohsiung and Tainan. Full-genome comparisons were conducted between 2023 strains and historical epidemic isolates.

RESULTS: A total of 26 706 laboratory-confirmed cases were reported, primarily in Tainan (80.7%) and Kaohsiung (11.9%). Real-time RT-PCR identified cocirculating DENV-1 and DENV-2 strains. Phylogenetic analysis confirmed the 2023 DENV-1 and DENV-2 strains were genetically linked to contemporary strains from Southeast Asian countries. Whole-genome sequencing identified several nonsynonymous mutations in the NS2A, NS3, and NS5 regions when compared with historical outbreak isolates. Time-lagged regression showed that imported cases, precipitation, and the BI were associated with incidence in univariate models. In Kaohsiung, the best-fitting multivariable model included the BI, but temperature and precipitation were the independent predictors. In Tainan, precipitation and, at longer lags, imported cases were more influential, while the BI lost significance after adjustment.

CONCLUSIONS: The 2023 dengue outbreak in Taiwan was driven by a complex interplay between viral introductions, climatic conditions, and vector dynamics. The differing transmission drivers observed between cities highlight the need for region-specific vector surveillance, climate-informed early warning systems, and sustained genomic monitoring to prevent future re-emergence of dengue in this non-endemic setting.

INTRODUCTION: Airborne particulate matter (PM), particularly fine (PM2.5) and coarse (PM10) particles, is a major environmental health concern linked to increased respiratory morbidity and mortality. During the COVID-19 pandemic, epidemiological studies suggested that PM exposure may worsen SARS-CoV-2 infection outcomes; however, cellular mechanisms underlying this association remain incompletely understood. Here, we investigated how pre-exposure to PM2.5 and PM10 impacts SARS-CoV-2 infection dynamics in Calu-3 human epithelial cells.

METHODS: Calu-3 cells were pre-exposed to PM for 72 h prior to infection with either the wild-type Wuhan strain or the more virulent Delta variant for additional 48 h. Viral infection, receptor expression, apoptosis and cytokine responses were assessed.

RESULTS: PM10, but not PM2.5, enhanced Delta variant infection, increasing the proportion of infected cells by 13.7% and viral titers by 2.6-fold compared with controls. This enhancement was not attributable to changes in ACE2 receptor expression or viral entry efficiency but instead impaired antiviral defenses. PM10 pre-exposure suppressed apoptosis and reduced the expression of pro-inflammatory cytokines including IFN-γ, IP-10, and TNF-α during Delta infection.

DISCUSSION: These findings suggest that PM10 compromise epithelial antiviral response by dampening apoptotic cell clearance and inflammatory responses, thereby creating a cellular condition more permissive to viral replication. Our study provides a mechanistic basis by which particulate air pollution may amplify SARS-CoV-2 pathogenicity in a variant-specific manner. These results underscore further validation in physiologically relevant systems and highlight the potential public health implications of air pollution during viral pandemics.

Originally identified in Kenya in 1921, African swine fever (ASF) primarily remained a sub-Saharan concern for nearly a century [...].

BACKGROUND: Taiwan experienced a major dengue outbreak in 2023 following the relaxation of COVID-19 border controls. The contributing factors remained unclear. This study investigated potential virological, immunological, and clinical drivers.

METHODS: We retrospectively analyzed laboratory-confirmed dengue virus (DENV) infections at a tertiary care hospital in southern Taiwan. Serotypes were identified by qRT-PCR. Viral origins were assessed through phylogenetic and envelope (E) gene amino acid analyses. Clinical features of DENV-1 and DENV-2 cases were compared. Neutralization and antibody-dependent enhancement (ADE) were evaluated using PRNT and ADE assays.

RESULTS: DENV-1 and DENV-2 were identified as the predominant circulating serotypes. Clinical analysis revealed that DENV-2 infection was significantly associated with older age, diabetes mellitus, hypertension, and elevated hematocrit levels (p < 0.05), and these associations remained statistically significant in multivariate analysis. Phylogenetic analysis showed that DENV-1 isolates belonged to genotypes I and IV, while DENV-2 strains were of the cosmopolitan genotype. These viruses clustered closely with strains from Southeast Asia. Amino acid analysis indicated that DENV-1 strains exhibited 2-10 substitutions relative to 2014 isolates, while DENV-2 strains closely matched those from 2015. Sera from the 2014-2015 outbreaks demonstrated potent homotypic but limited heterotypic neutralization. ADE was observed in heterotypic infection contexts.

CONCLUSIONS: The 2023 dengue outbreak in Taiwan was driven by co-circulation of DENV-1 and DENV-2, limited heterotypic immunity, and ADE. These findings highlight the importance of integrated virological surveillance, genotype monitoring, and immunological assessment to inform dengue control strategies in non-endemic regions experiencing imported viral threats.

BACKGROUND: Strengthening mRNA vaccine development in LMICs is essential for enhancing global pandemic preparedness. This study evaluated the safety and immunogenicity of Comvigen, a bivalent SARS-CoV-2 vaccine, in comparison to the Comirnaty bivalent vaccine (Comirnaty).

METHODS: This phase II, randomised, open-label, non-inferiority trial was conducted in Thailand across four centres. Participants (n = 450) were randomly assigned (2:1) to receive either Comvigen (50 μg) or Comirnaty (30 μg), using block randomisation (size = 9). Eligible participants had completed at least 2 doses of any approved COVID-19 vaccine, with the last mRNA-vaccine dose given over 3 months before enrolment. The non-inferiority margin of a geometric mean ratio (GMR) of 0.67. The primary immunogenicity endpoint was pseudovirus neutralisation titres (psVNT-50) against SARS-CoV-2 wild-type and Omicron BA.4/BA.5 at Day 29. Safety outcomes included local and systemic adverse reactions up to six months post-vaccination. Immunogenicity analyses were conducted on the Per-Protocol (PP) population and the modified Intent-to-Treat (mITT) population; safety analyses included all participants. Laboratory personnel were blinded to vaccine assignment (ClinicalTrials.gov: NCT05930730).

FINDINGS: Between October and November 2023, 450 participants were enrolled (median age of 36 years, IQR 30-45). At day 29, the geometric mean titre (GMT) of psVNT-50 against wild-type virus increased from 475.9 to 2062.9 for Comvigen and from 458.8 to 1905.1 for Comirnaty (GMR 1.1, 95% CI: 1.0-1.2), meeting non-inferiority criteria. Against Omicron BA.4/BA.5, GMTs were 3909.8 for Comvigen and 3288.6 for Comirnaty (GMR 1.2, 95% 1.0-1.4). Local and systemic reactions were more frequent with Comvigen (91% vs. 78%, p = 0.0002, 79% vs. 70%, p = 0.028) but were mild or moderate and transient with no difference in fever (6% vs. 5%, p = 0.84).

INTERPRETATION: Comvigen demonstrated non-inferiority immunogenicity to Comirnaty and had a comparable safety profile, supporting mRNA vaccine development for global access and pandemic preparedness.

FUNDING: Covid-19 Pandemic Emergency Fund granted by Thailand's National Economic and Social Development Council provided major funding. Supplementary funding was provided by National Vaccine Institute (NVI), Thailand; Center of Excellence in Vaccine Research and Development (Chula VRC), Faculty of Medicine, Chulalongkorn University; Chulalongkorn University Second Century Fund (C2F); BioNet-Asia and Public Donation through Covid-19 vaccine development fund of the Faculty of Medicine, Chulalongkorn University and the Thai Red Cross Society, Thailand.

Severe diseases like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak urge efficient discovery of drugs for emergent needs and precision medicine. This study demonstrates an interdisciplinary solution by identification of a chief anti-SARS-CoV-2 small molecule, 2,3,5,8-tetrahydroxy-6-methylnaphthalene-1,4-dione (TMD) from a Taiwanese traditional medicine, Antrodia cinnamomea. TMD was found to inhibit the key viral replication enzymes, 3-chymotrypsin-like protease (3CLpro) and papain-like protease (PLpro), by structure-based prediction analysis using the Explore program of BT&D2 drug targeting system. Subsequently, TMD was total-synthesized and shown to inhibit Omicron BA.2 and BA.5 variants. The enzymatic inhibition kinetics studies revealed the competitive inhibition and dual-target nature of TMD and its potential capability to target the proteases in mixed-type mode, consistent with the in silico mechanistic analysis. The predicted less off-target side effects of TMD also agreed with the animal toxicity test result of no apparent toxicity. This study provides new insight into anti-viral mechanism of Antrodia cinnamomea and a new lead drug with improved pharmacokinetics to combat SARS-CoV-2 infection.

This study explores immune responses in mild Omicron-era COVID-19 breakthrough cases, focusing on cytokine dysregulation, antibody dynamics, and Long COVID. Samples from 114 mild COVID-19 patients across multiple waves were analyzed at three timepoints (T1: 2-4 weeks, T2: 3-4 months, T3: 6-8 months post-infection). Persistent IP-10 elevation up to 8 months suggests prolonged low-grade immune activation. Hybrid immunity from Omicron breakthrough infections provided broad cross-variant antibody recognition but showed declining neutralization over time. Among vaccination regimens, mRNA-inclusive combinations were associated with lower Long COVID scores. CoV-229E antibody levels correlated with Long COVID scores. These findings underscore the need for extended monitoring of mild COVID-19 cases and highlight the potential of mRNA vaccines in reducing post-COVID-19 complications. Insights into immune alterations and vaccine effects can inform the development of future vaccination strategies and approaches for managing post-COVID-19 conditions.

Galectins are a family of β-galactosides-binding protein, crucial regulators of host-virus interactions. They achieve this by recognizing specific glycan patterns on viral surfaces or mediating interactions with intracellular viral or host proteins, subsequently influencing the critical phases of the viral life cycle, such as attachment, replication, immune evasion, and reactivation. Furthermore, galectins modulate host immune responses, shaping the progression and outcomes of viral infections. This review comprehensively examines the roles of both endogenous and exogenous galectins in viral infections, noting that only a few galectins, including Galectin-1, -3, -4, -7, -8, and - 9, Have been identified as key players in viral infection. Notably, Galectin-1, -3, and - 9 play diverse functions in both DNA and RNA viral infection. Emerging evidence highlights the potential of Galectin-4 and -8 as intracellular sensors and modulators of viral pathogenesis. Endogenous galectins, produced by host cells, act through both glycan-dependent and glycan-independent mechanisms, influencing viral processes and immune responses. Exogenous galectins, which are secreted by other cells or administered as recombinant proteins, can either enhance or counteract the actions of endogenous galectins. The functions of galectins are virus-specific and context-dependent, serving as either promoters or inhibitors of viral replication and reactivation. Dysregulation of galectin expression is often linked to disease progression, highlighting their potential as diagnostic and prognostic biomarkers, as well as therapeutic targets. The important and varied roles that galectins play in viral infections are highlighted in this review, which also provides fresh insights into host-pathogen interactions and the development of antiviral tactics.

Monkeypox virus (Mpox) has been recognized for causing distinct skin lesions and is primarily transmitted through skin and sexual contact. To date, the transmissibility and pathogenesis of the Mpox virus in distal human lung has never been completely explored. Here the transmission pathways and Mpox tropism on patient-derived air-liquid epithelium (ALE) model fabricated using isolated primary human alveolar epithelial cells (hAECs) were investigated. hAECs were cultured and exposed to the Mpox virus clade IIb isolated from patient. DNA, proteins, and the tropism were elucidated using polymerase chain reaction (PCR), Western blot and high-content fluorescent imaging. Transmission electron microscopy (TEM) was employed to systematically observe the cellular distribution of viral particles. Viral titers were determined by TCID50 assay. Innate immune response and inflammatory mediators were measured using Milliplex® multiplex and ELISA analysis. Pathology at alveolar barrier integrity was determined using transepithelial electrical resistance (TEER) analysis. The study included mock-infected cells as control. Mpox virus significantly infected 42.82% of total hAEC populations. The prominent observed pathology included a significant reduction in TEER values, loss of tight junction protein, presence of tunneling nanotubes (TNTs) and syncytium morphology. Four stages of Mpox biogenesis were clearly observed without significant activation of IL-6, MIP1alpha, TNF-α, and Galectin-9, although IL-1β were subtly promoted. The developed patient-derived ALE is a versatile model for Mpox virus clade IIb infection reflecting respiratory transmission competence of the Mpox. Postinfection lung pathogenesis demonstrated alveolar barrier damage without significant inflammation, raising concerns about possible immune evasion by the virus.