Background: China's influenza vaccine (InfV) has undergone multiple iterations and numerous technological breakthroughs, providing tremendous impetus and solid support for the development of China's health sector. As the number of vaccinated individuals continues to rise, the importance of ongoing surveillance and evaluation of vaccine safety has become increasingly prominent, forming part of efforts to maintain public trust in the national immunization program and ensure its sustainability. Methods: From 2016 to 2025, data on suspected adverse events following immunization (AEFIs) related to InfV administration were extracted from the Chinese National Immunization Information System (CNIIS). Data on InfV vaccination doses were obtained from the Anhui Provincial Immunization Information Management System. A descriptive statistical method was used to analyze the distribution characteristics of AEFIs, and the chi-square test was applied to evaluate differences in reporting rates. Results: Between 2016 and 2025, a total of 4026 AEFI reports related to InfV were monitored through the CNIIS. The overall reporting rate was 34.40 per 100,000 doses. Specifically, common adverse reactions and rare adverse reactions accounted for 95.88% (3860 cases) and 3.38% (136 cases), with reporting rates of 32.98 per 100,000 doses and 1.16 per 100,000 doses, respectively. Among common adverse reactions, the reporting rates of fever (axillary temperature ≥ 38.6 °C), local redness and swelling at the injection site (diameter > 5.0 cm), and local induration (diameter > 5.0 cm) were 9.62 per 100,000 doses, 1.96 per 100,000 doses, and 1.20 per 100,000 doses, respectively. Among rare adverse reactions, the reporting rates of allergic rash, angioedema, anaphylactic shock, febrile convulsions, anaphylactoid purpura, thrombocytopenic purpura, epilepsy, Guillain-Barré syndrome, and aseptic abscess were 0.98, 0.05, 0.03, 0.03, 0.02, 0.02, 0.01, 0.01, and 0.01 per 100,000 doses, respectively. No cases were reported for subunit inactivated influenza vaccine (IIV, Subunit). Statistically significant differences were observed in the reporting rates of allergic rash across different types of InfV (χ[2] = 36.83, p < 0.05), with trivalent inactivated influenza vaccine (IIV3, Split) and trivalent live attenuated influenza virus vaccine (LAIV3) showing the highest reporting rates. Most adverse events following vaccination occurred within 24 h after inoculation. Conclusions: From 2016 to 2025, the overall reporting rate of AEFIs after InfV administration in Anhui Province was within an acceptable range. Common adverse reactions were common, while rare adverse reactions were few, mainly consisting of allergic reactions. These results indicate that InfV has a favorable safety profile, and continuous strengthening of AEFI surveillance for InfV and improvement of surveillance quality are warranted.

Background/Objectives: African Swine Fever (ASF) represents one of the most serious threats to animal health and global food security. The causative agent of ASF is the African swine fever virus (ASFV), a DNA virus belonging to the Asfarviridae family. Here, we describe ex vivo results for an original anti-ASFV vaccine approach based on the cellular immune response induced by extracellular vesicles (EVs) engineered to express four ASFV proteins. EV engineering was achieved by expressing a DNA vector encoding a biologically inactive HIV-1 Nef protein (Nef[mut]), which exhibits unusually high efficiency of incorporation into EVs, even when fused to foreign proteins. Previous studies have demonstrated that intramuscular injection of Nef[mut]-based vectors leads to the engineering of Evs, spontaneously released by muscle cells, and induction of antigen-specific CD8[+] T cell immunity. Methods: We designed DNA vectors expressing the fusion products between Nef[mut] and each of the four ASFV structural proteins p30, p54, pp62, and p72. Engineered EVs were molecularly characterized by Western blot and nanotrack analysis, and their potential immunogenicity was assessed by priming and cross-presentation assays. Results: We assessed that the four fusion proteins were successfully expressed in transfected mammalian cells, with the release of valuable amounts of engineered EVs. When immature swine dendritic cells were challenged with the engineered EVs and then co-cultivated with autologous peripheral blood lymphocytes in priming assays, lymphocyte subpopulations specifically reacting against each ASFV antigen were elicited, as detected by an IFN-γ ELISpot assay. In addition, we provide evidence that the Nef[mut]-based fusion products incorporated into the engineered EVs can be cross-presented by professional antigen-presenting cells, leading to cross-priming of autologous lymphocytes. Conclusions: These results represent the best premise to go forward with experiments examining immunogenicity and antiviral efficiency in pigs.

West Nile Virus (WNV) belongs to the orthoflavivirus genus and is part of the Flaviviridae family, which includes the Japanese encephalitis virus, Dengue virus, Zika virus, and yellow fever virus. WNV circulates among birds and mosquitoes, posing infection risks to humans and mammals. The significant rise in WNV's geographic spread and infection rates over the past five decades has prompted urgent public health concerns, driving the need for accelerated vaccine research. The development of a vaccine for WNV infection presents several challenges, primarily due to the virus's complex biology, the risk of cross-reactivity with other flaviviruses, safety concerns such as antibody-dependent enhancement (ADE), and the economic and logistical hurdles in vaccine production. Despite significant research efforts, no human vaccine has been approved, although several candidates are in various stages of development. The current review offers a comprehensive summary of the latest progress and the concomitant challenges in the development of vaccines. It also discusses the role of host-pathogen interaction, host immunity, viral immune evasion, and disease pathogenesis in facilitating the advancement of vaccines.

Background:Borrelia miyamotoi is an emerging tick-borne pathogen causing relapsing fever in humans. Although Saint Petersburg and the surrounding Leningrad Oblast harbor a high abundance of ixodid ticks (I. ricinus, I. persulcatus), no integrated assessment has yet simultaneously addressed pathogen circulation in vectors, reservoir hosts, and human populations in this specific northwestern region of Russia. Methods: During 2022-2024, we collected 1518 questing adult ticks and trapped 516 small mammals in Saint Petersburg and Leningrad Oblast. B. miyamotoi DNA was detected by real-time PCR. Sera from 3743 randomly selected volunteers (1553 from Saint Petersburg, 2190 from Leningrad Oblast) were tested for anti-B. miyamotoi IgG/IgM using a protein microarray (antigens: GlpQ, Vmps, flagellin). Infection rates and seroprevalence with 95% Wilson confidence intervals were compared using chi-square tests. Results: The overall tick infection rate was 3.78% (57/1506). I. ricinus had a significantly higher prevalence (4.94%; 95% CI: 3.67-6.60%) than I. persulcatus (2.29%; 95% CI: 1.39-3.74%; p = 0.011). Ticks from Leningrad Oblast also showed markedly elevated infection rates (4.98%; 95% CI: 3.75-6.58%) compared to those from Saint Petersburg (1.89%; 95% CI: 1.06-3.35%; p = 0.004). Small mammals exhibited substantially higher infection rates in Leningrad Oblast (39.44%; 95% CI: 31.78-47.65%) than in Saint Petersburg (13.90%; 95% CI: 10.76-17.78%; p < 0.001). Bank voles (Myodes glareolus) and yellow-necked mice (Apodemus flavicollis) were the main reservoirs; synanthropic rodents trapped within the city were found to be infected for the first time. No significant organotropism was detected, but positive correlations between infection in the heart, liver, and kidney suggested hematogenous dissemination. The overall human seroprevalence of B. miyamotoi was 1.71% (95% CI: 1.34-2.18%) and was significantly higher in Leningrad Oblast (2.19%; 95% CI: 1.66-2.89%) than in Saint Petersburg (1.03%; 95% CI: 0.64-1.67%; p = 0.010). In contrast, the seroprevalence of B. burgdorferi s. l. did not differ between the two regions (approximately 5.1%). Conclusions: This first comprehensive, multi-level investigation in Saint Petersburg and Leningrad Oblast reveals a stable epidemiological gradient: natural foci in Leningrad Oblast sustain higher B. miyamotoi circulation in ticks and rodents, which translates into a two-fold higher exposure of the rural population. The findings highlight the need to include B. miyamotoi in regional tick-borne infection surveillance programs and to adopt differentiated risk assessment strategies for urban and rural settings.

Spotted fever group (SFG) rickettsioses are emerging zoonotic diseases of increasing relevance in Latin America, yet the specific species involved in human infections remain poorly defined in many endemic regions. This study aimed to determine the most probable antigen among SFG-seroreactive febrile patients from Villeta, Colombia. A panel of 25 convalescent-phase serum samples previously identified as positive for SFG Rickettsia spp. antibodies was analyzed by indirect immunofluorescence assay using antigens of Rickettsia rickettsii, R. amblyommatis and R. parkeri. Antibody titers were compared to identify differential seroreactivity patterns. Overall, 44% (11/25) of the samples showed differential antibody titers against one of the tested antigens. Among these, nine (36%) exhibited higher titers to R. parkeri and two (8%) to R. amblyommatis, while none showed exclusive reactivity to R. rickettsii. The remaining 56% (14/25) presented similar titers across antigens, consistent with indeterminate or cross-reactive SFG responses. Antibody titers ranged from 1:128 to 1:4096, with R. parkeri showing the strongest reactivity. These findings suggest R. parkeri or a highly related Rickettsia species as the predominant probable antigen in Villeta, highlighting its potential role in mild rickettsial infections and emphasizing the need for eco-epidemiological studies to identify local vectors and reservoirs.

Background: Crimean-Congo hemorrhagic fever virus (CCHFV) is an important tick-borne zoonosis and an emerging public health threat across Africa. Although evidence of viral circulation is mounting, information remains fragmented, limiting a comprehensive understanding of transmission ecology, regional hotspot heterogeneity, and preparedness needs across the continent. Methods: This narrative review critically synthesized published literature on CCHFV in Africa, identified through PubMed, Scopus, and Google Scholar and supplemented by citation tracking and authoritative public health reports. Evidence from epidemiological, ecological, molecular, surveillance, and One Health studies was integrated to examine transmission dynamics, geographic hotspot distribution, viral diversity, risk factors, diagnostic and surveillance challenges, and preparedness strategies. Results: Available evidence shows marked geographic heterogeneity in CCHFV transmission across Africa, with hotspot regions shaped by ecological suitability, Hyalomma tick distribution, livestock-human interactions, and health system capacity. Livestock consistently show higher exposure than humans, underscoring their role as key indicators of viral circulation. Diagnostic limitations, passive surveillance, ecological variability, and serological cross-reactivity contribute to substantial under recognition of disease burden, while molecular studies reveal considerable viral diversity and ongoing evolution across African regions. Conclusions: CCHFV remains underdiagnosed and underreported in many African settings because of limited surveillance and diagnostic capacity. Strengthening integrated One Health surveillance, expanding laboratory and genomic capacity, utilizing livestock as sentinel populations, and improving cross-sectoral collaboration are critical for enhancing early detection, outbreak preparedness, and effective public health response across the continent.

Orthohantaviruses are zoonotic pathogens belonging to the family Hantaviridae and are responsible for significant human disease. These infections are characterized by acute systemic illness, vascular dysfunction, and, in severe cases, hemorrhage and multiorgan failure. Depending on the viral species involved, infection may result in hemorrhagic fever with renal syndrome (HFRS) or hantavirus cardiopulmonary syndrome (HCPS), both of which are associated with substantial morbidity and mortality. Rodents act as natural reservoirs, maintaining viral persistence in endemic ecosystems and enabling sporadic spillover to humans through exposure to infected excreta or contaminated environments. This review synthesizes current knowledge on rodent reservoir competence, hantavirus replication strategies, pathogenesis, clinical manifestations, ecological drivers of transmission, public health implications and future therapeutic developments and challenges. Understanding these mechanisms is essential for enhancing surveillance, risk assessment, and preventive strategies against orthohantavirus infections.

Orthoebolavirus causes severe Ebola virus disease (EVD) and deadly outbreaks in humans. This infection occurs through macropinocytosis and trafficking to late endosomes or lysosomes that utilize the receptor Niemann-Pick C1 (NPC1) to enter the cell cytoplasm. We designed peptide inhibitors based on the NPC1 receptor to target the NPC1 binding site to block viral entry. The results indicated that the ligand-based peptide inhibitors showed potent inhibition activities in vitro studies against pseudotyped or replication-competent Orthoebolavirus. Therefore, we further evaluated one of them in a mouse model challenged with mice-adapted Ebola viruses, which showed some protection efficacy compared with the control group. This study suggests that ligand-based peptides are encouraging inhibitors in the development of inhibitors against Ebola virus infection.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne zoonotic disease of significant public health concern, particularly in endemic regions. However, data on the distribution and circulation of Crimean-Congo hemorrhagic fever virus (CCHFV) in animal populations remain limited, despite their importance for assessing virus circulation and infection patterns. A cross-sectional seroepidemiological study was conducted in North Macedonia (N. Macedonia) to determine the seroprevalence rates of CCHFV in small ruminants and to identify areas at increased risk of virus circulation. A total of 1992 sera samples from sheep and goats were tested for Crimean-Congo hemorrhagic fever virus (CCHFV) antibody using a commercial enzyme-linked immunosorbent assay (ELISA). Data on species, age, animal origin, and risk factors (questionnaire) were collected and analyzed. Overall, true seroprevalence, calculated by adjusting the apparent seroprevalence according to the diagnostic performance of the ELISA assay in order to estimate the actual prevalence in the studied population, was 25.02% (493/1992; 95% CI 23.11-26.94). Sheep showed higher seroprevalence rates, 27.34% (397/1452; 95% CI 25.11-29.69), compared to goats, 17.78% (96/540; 95% CI 14.78-21.23). Seroprevalence rates varied markedly across regions, ranging from 2.41% to 49.80%, with the highest values observed in the Eastern and Vardar regions. Seroprevalence rates increased with age, reaching the highest values in animals aged ≥ 5 years, 27.27% (81/297; 95% CI 22.52-32.60). Small ruminants, particularly sheep, may serve as useful indicators for defining the high-risk areas for CCHFV transmission, providing valuable support for a One Health approach.

Orthohantavirus infections are classically associated with hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus cardiopulmonary syndrome (HCPS) in the Americas. However, accumulating evidence indicates that the clinical spectrum is considerably broader, with frequent involvement of organ systems beyond the kidney and lung. Hepatic manifestations, in particular, may mimic acute viral hepatitis, leading to diagnostic challenges and underrecognition. This paper synthesizes published evidence on hepatic involvement in orthohantavirus infection, with a focus on clinical presentation, pathogenic mechanisms, differential diagnosis, biomarkers, and public health implications. Relevant literature was identified through searches of peer-reviewed articles, with emphasis on studies reporting hypertransaminasemia, hepatitis-like illness, and liver injury in confirmed hantavirus infections. Mild to moderate elevations in aminotransferases are common during acute orthohantavirus infection, and in some patients the clinical picture may be dominated by fever, thrombocytopenia, and hepatitis-like abnormalities, closely resembling dengue, leptospirosis, or classical viral hepatitis. Hepatic injury appears to result primarily from systemic endothelial dysfunction, immune-mediated inflammation, and microvascular leakage rather than direct hepatocytopathic effects. Emerging biomarkers of severity, including thrombocytopenia, neutrophil-to-lymphocyte ratio, soluble thrombomodulin, and IL-6 trans-signaling, reflect widespread vascular and inflammatory activation. Diagnostic delays are frequent, particularly in non-endemic regions, due to low clinical awareness and overlapping features with more common febrile hepatotropic syndromes. Orthohantavirus infection should be considered in the differential diagnosis of acute febrile illness with unexplained hypertransaminasemia and thrombocytopenia, especially when epidemiological clues suggest rodent exposure or compatible environmental contexts. Recognizing hepatic involvement as part of a systemic endothelial syndrome may improve diagnostic accuracy, reduce underreporting, and facilitate earlier supportive management. Increased awareness among hepatologists, infectious disease specialists, and emergency physicians is warranted.

Hantaviruses are emerging zoonotic pathogens responsible for two severe clinical syndromes: (i) haemorrhagic fever with renal syndrome (HFRS) and (ii) hantavirus cardiopulmonary syndrome (HCPS), collectively causing more than 200,000 human cases annually worldwide. Despite their public-health importance, the molecular mechanisms governing the host response and the population-level dynamics of rodent-to-human spillover remain incompletely characterised. The timeliness of this framework is underscored by the April-May 2026 outbreak of Andes orthohantavirus aboard the MV Hondius cruise ship, the first such cluster in a maritime setting, with three deaths reported across multiple countries. This event revealed critical gaps in existing models that treat humans solely as dead-end spillover hosts. Our coupled Susceptible-Exposed-Infectious-Recovered-Dead (SEIRD) model assumes no human-to-human transmission and is therefore designed for hantavirus strains where spillover does not lead to secondary human cases, specifically Hantaan virus (HTNV), Puumala virus (PUUV), Sin Nombre virus (SNV), and Dobrava-Belgrade virus (DOBV). The Andes virus (ANDV) outbreak aboard the MV Hondius is used as a real-world case study to assess the boundaries of our model and to motivate future extensions, not as a direct validation target for its quantitative predictions. Here, we present an integrated computational study combining three complementary analyses. First, we performed a preliminary phylogenetic analysis of the viral sequence, identifying Orthohantavirus andesense as the likely etiological agent responsible for the vessel-associated outbreak. Second, we carried out a downstream transcriptomic analysis of Hantaan virus (HTNV)-infected human umbilical vein endothelial cells (HUVECs), using publicly available RNA-seq data (GEO accession GSE133751, n=3 per group). This analysis identified 184 upregulated and 19 downregulated genes, highlighting a transcriptional response dominated by interferon-stimulated genes (ISGs), including CXCL10, CXCL11, MX2, DDX58, IRF7, STAT1, OASL, and CMPK2. We then constructed a protein-protein interaction (PPI) network using STRING, comprising 176 nodes and 3210 edges, and applied a composite network centrality score to rank putative regulatory hubs. This analysis identified ISG15, IRF1, CXCL10, STAT1, and DDX58 as the most central nodes. Pathway enrichment analysis confirmed a strong activation of interferon signalling (Reactome, p=1.3×10-63), antiviral defence mechanisms (Gene Ontology, p=3.8×10-58), and NF-κB-related pathways, together with a concurrent suppression of ribosomal translation. Finally, we developed a coupled SEIRD epidemiological model that explicitly represents rodent-to-rodent and rodent-to-human transmission with logistic rodent population growth. Preliminary simulation analysis demonstrates that reducing human exposure to rodent excreta is substantially more effective than rodent population control alone for reducing human disease burden, and that rodent control in isolation can paradoxically increase human cases through a dilution-like effect. The integrated framework provides molecular and epidemiological insights relevant to hantavirus surveillance, therapeutic target identification, and public-health intervention design.

Typhus (FBT), caused by Rickettsia typhi, rarely causes neurological disease. Herein, we describe neurological involvement in two cases of FBT. In the first case, an adult presented with persistent fever which deteriorated into status epilepticus. He was successfully treated with doxycycline and made a complete recovery. In the second case, a patient suffered an ischemic stroke and had a protracted clinical course but ultimately made a near complete recovery. In addition to these cases, we conducted a comprehensive narrative review of 43 cases of neurologic involvement in FBT reported from 1989 to 2025. Cases were excluded if there were pathologic discrepancies with typical cases of FBT. Presentations ranged from cranial nerve palsies to meningitis and fulminant encephalitis. This review highlights the spectrum of CNS complications associated with FBT and underscores the importance of early recognition and treatment with doxycycline to improve outcomes. Given the potential severity of neurologic involvement, clinicians in endemic areas should maintain a high index of suspicion for FBT in patients presenting with a febrile illness and neurologic symptoms.