Biosafety and Health最新文献

The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.

Enterovirus D68 (EV-D68) infection causes severe acute respiratory infection and severe neurological complications, such as acute flaccid myelitis (AFM), in children. However, although EV-D68 has pandemic potential, no effective drugs or vaccines are currently clinically available. Furthermore, EV-D68 infection-induced inflammatory response and cell death are not fully understood. In this study, we demonstrated that several inflammatory cytokines were upregulated in a multiplicity of infection (MOI) dependent manner in EV-D68-infected human rhabdomyosarcoma (RD) cells. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) confirmed that tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), C-C motif chemokine ligand-5 (CCL-5), and CXC motif chemokine ligand-5 (CXCL-5) mRNA levels were highly upregulated after EV-D68 infection. IL-1β processing and maturation mediated by caspase-8 was inhibited by the caspase-8 inhibitor Z-IETD-FMK. EV-D68 infection activates caspase-8 to mediate IL-1β maturation and secretion. Additionally, EV-D68 activated cell death-related proteins such as caspase-3, poly (ADP-ribose) polymerase 1 (PARP-1), phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL), and gasdermin E (GSDME). Thus, EV-D68 infection activates caspase-8, which triggers the necroptosis and apoptosis pathways. Overall, our data suggest that caspase-8 activation is associated with the inflammatory response and cell death in EV-D68-infected RD cells. This mechanism represents a novel target for the treatment of EV-D68 infection by inhibiting caspase-8 activation.

Since the outbreak of the coronavirus disease 2019 (COVID-19) epidemic in 2019, the public health system has faced enormous challenges. Tracking the individuals who test positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key step for interrupting chains of transmission of SARS-CoV-2 and reducing COVID-19-associated mortality. With the increasing of asymptomatic infections, it is difficult to track asymptomatic infections through epidemiological surveys and virus whole-genome sequencing. However, due to the cross-reactivity of neutralizing antibodies produced by multiple virus subtypes, neutralizing antibody detection cannot be used to determine whether an individual has a history of infection with a specific subtype of SARS-CoV-2. We recruited 4 human leukocyte antigen A2 (HLA-A2) infections, 15 individuals who received three doses of inactivated vaccines, and 30 breakthrough infections after vaccination and discussed a case-tracking approach to detect epitope-specific CD8⁺ T cells in the peripheral blood of close contacts, including accurate HLA typing based on ribonucleic acid (RNA)-sequencing and flow cytometry data and the comparison and characterization of SARS-CoV-2 HLA-A2 and HLA-A24 epitope-specific CD8⁺ T cells. From individuals who received three doses of inactivated vaccine, we observed that the CD8⁺ T cell specificity for ancestral epitopes was significantly higher than for mutated epitopes, and the fold change of CD8⁺ T cells corresponding to mutated epitopes relative to ancestral epitopes was less than 1. The enzyme-linked immunospot (ELISpot) results further validate this result. This study forms a “method for understanding the infection history of SARS-CoV-2 subtypes based on the proportion of epitope-specific CD8⁺ T cells in the peripheral blood of subjects”, covering up to 46 % of the population, including HLA-A2⁺ and HLA-A24⁺ donors, providing a novel method for SARS-CoV-2 infected case tracing.

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

Ceftazidime-avibactam (CZA) is a recently approved combination synthetic β-lactamase inhibitor used in human clinical medicine. Cases of CZA resistance in humans have already been reported, but limited research has investigated CZA resistance in pets. This study explored the prevalence and transmission of CZA-resistant Escherichia coli (CZAREC) among pets, their owners, veterinarians, and the environment in animal hospitals. A total of 5,419 clinical samples were collected from dogs and cats, along with samples from the environment (n = 5,843), veterinarians (n = 557), and pet owners (n = 368) in animal hospitals. From these samples, 760 Escherichia coli (E. coli) isolates were obtained, out of which 60 were identified as CZAREC. These included 34 isolates from the environment (9.14 %, n = 372), three from veterinarians (8.11 %, n = 37), and 23 from animals (6.82 %, n = 337). No CZAREC isolates were found in pet owners. The predominant sequence types of CZARECs were ST156 (n = 20), ST410 (n = 19) and ST101 (n = 7). Bayesian analysis revealed six clusters comprising 47 isolates from the hospital environment, pets, and veterinaries, displaying genetic relatedness of less than 100 core genome single nucleotide polymorphisms (cgSNPs) between any two isolates in each cluster. Some CZAREC isolates with high genetic similarity persisted in the same animal hospital for four to six months. Moreover, discriminant analysis of principal components indicated that most isolates from different hosts shared a genetic source in the human/dog/cat merged cluster. Overall, evidence of CZARECs transmission was found among pets, the environment, and veterinarians in animal hospitals. The findings emphasize the importance of monitoring CZARECs in the veterinary clinical setting to ensure the health of both pets and humans.

Mpox is a zoonotic infectious disease caused by the mpox virus (MPXV). Historically, the majority of mpox cases have been documented in Central Africa. However, since May 2022, there has been a notable rise in reported cases from regions beyond Africa. Currently, over 110 countries spanning Europe, North America, South America, Asia, and other territories have reported mpox infections. This report details a case involving a patient who identifies as a man who has sex with men (MSM) and is concurrently infected with MPXV, human immunodeficiency virus type 1 (HIV-1), Pneumocystis jiroveci, as well as extensively drug-resistant tuberculosis (XDR-TB). This patient had also received a vaccination for smallpox in the past. Additionally, we provide photographic documentation charting the progression of dermatological manifestations associated with mpox. This case highlights the significance of sexual intercourse as a crucial mode of transmission for mpox. The rapid and widespread dissemination of the MPXV across various regions, especially among MSM communities, underscores the importance of enhancing preventive education efforts targeted at high-risk populations.

Chicken is an important food animal worldwide and plays an important role in human life by providing meat and eggs. Despite recent significant advances in gut microbiome studies, a comprehensive study of chicken gut bacterial, archaeal, and viral genomes remains unavailable. In this study, we constructed a chicken multi-kingdom microbiome catalog (CMKMC), including 18,201 bacterial, 225 archaeal, and 33,411 viral genomes, and annotated over 6,076,006 protein-coding genes by integrating 135 chicken gut metagenomes and publicly available metagenome-assembled genomes (MAGs) from ten countries. We found that 812 and 240 MAGs in our dataset were putative novel species and genera, respectively, far beyond what was previously reported. The newly unclassified MAGs were predominant in Phyla Firmicutes_A (n = 263), followed by Firmicutes (n = 126), Bacteroidota (n = 121), and Proteobacteria (n = 87). Most of the classified species-level viral operational taxonomic units belong to Caudovirales. Approximately, 63.24 % of chicken gut viromes are predicted to infect two or more hosts, including complete circular viruses. Moreover, we found that diverse auxiliary metabolic genes and antibiotic resistance genes were carried by viruses. Together, our CMKMC provides the largest integrated MAGs and viral genomes from the chicken gut to date, functional insights into the chicken gastrointestinal tract microbiota, and paves the way for microbial interventions for better chicken health and productivity.

In response to problems of poor sampling quality, low sensitivity, and high demand for medical personnel regarding the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) oropharyngeal (OP) swab sampling used in China, we aimed to evaluate the diagnostic performance and acceptability of saliva-based nucleic acid amplification tests (NAATs) in China. The results showed that, using nasopharyngeal (NP) swab results as the gold standard, the overall sensitivities for saliva specimens and OP swabs were 93.3 % and 85.0 %, the specificities were 92.6 % and 93.8 %, respectively. The results of an acceptability survey showed that the scores for saliva, OP, and NP samples were 9.46 ± 1.69, 8.11 ± 2.42, and 4.58 ± 3.82 out of 10, respectively, with significant differences among the three groups (P < 0.05). With higher sensitivity, comparable specificity, and strong public preference, saliva-based NAATs represent a convenient and effective method for detecting SARS-CoV-2 in future epidemics.

Uganda has been implementing the Global Health Security Agenda (GHSA) since 2015 to build its capacity according to World Health Organization (WHO) Benchmarks on International Health Regulations Capacities. The country remains prone to outbreaks, with more than 20 disease outbreaks reported in the past five years, including Ebola virus disease, Crimean-Congo haemorrhagic fever, Marburg haemorrhagic fever, measles, yellow fever, coronavirus disease 2019 (COVID-19), and cholera. Antimicrobial resistance (AMR) is an ongoing challenge. Uganda scored capacity level 3 on infection prevention and control (IPC) and antimicrobial stewardship (AMS) in the 2017 Joint External Evaluation (JEE) assessment. Identified gaps were being addressed after a self-assessment in 2021. This paper describes the technical assistance approaches provided to Uganda by the Medicines, Technologies, and Pharmaceutical Services Program, funded by the United States (U.S.) Agency for International Development, and implemented by Management Sciences for Health. The program, through a One Health approach, supported systematic capacity strengthening based on the JEE’s capacity advancement framework for global health security, specifically relating to AMR. The program’s interventions impacted 32 WHO benchmark actions (7 for AMR multisectoral coordination, 16 for IPC, and 9 for AMS), contributing to Uganda’s strengthened GHSA capacity. Leveraging success built on the AMR platform, the program trained 745 health workers in IPC for the Ebola virus and provided support for simulation exercises by eight district IPC teams. The program also worked with the Ministry of Health to coordinate IPC for the COVID-19 response in five health regions, covering 45 districts and reaching 5,452 health workers at 858 health facilities.

The status of coinfection during the national outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.5.2 or BF.7 in China in the winter of 2022, which is suspected to contribute substantially to the overloaded severe cases, needs to be investigated. We analyzed the coinfection status of 385 severe patients infected with the Omicron variant in Guangzhou using metagenomic sequencing. We found that 317 (82.3 %) patients were coinfected with at least one additional pathogen(s), including bacteria (58.7 %), fungi (27.1 %) and viruses (73.5 %). Pseudomonas aeruginosa (P. aeruginosa) (24.2 %), Staphylococcus aureus (S. aureus) (14.0 %), and Klebsiella pneumoniae (K. pneumonia) (13.4 %) ranked as the top three coinfected bacteria. Aspergillus fumigatus (A. fumigatus) (39.5 %), Pneumocystis jirovecii (P. jirovecii) (24.4 %) and Canidia albicans (C. albicans) (22.1 %) were the top three coinfected fungi. Epstein-Barr virus (EBV) (63.1 %), Human herpesvirus 7 (HHV-7) (34.8 %), and Herpes simplex virus 1 (HSV-1) (32.6 %) were the top three coinfected viruses. Of note, the detection of multiple coinfections of potential pathogenic bacteria, fungi, and viruses, despite lacking consistent patterns, highlighted a complicated synergistic contribution to disease severity. Our study presents the most comprehensive spectrum of bacterial, fungal, and viral coinfections in Omicron-associated severe coronavirus disease 2019 (COVID-19), implying that the coinfection of conditional pathogens might synergistically deteriorate the Omicron infection outcomes.