Biosafety and Health最新文献

Human adenoviruses (HAdVs) are major respiratory pathogens. Specifically, human adenovirus type 4 (HAdV4) and human adenovirus type 7 (HAdV7) are known for causing fever and pneumonia, with documented cases of fatalities among the population. In recent years, HAdV4/HAdV7 has been implicated in causing substantial outbreaks, leading to increased morbidity in multiple countries. Most HAdV4 and HAdV7 infections have been reported in North America, Asia, Europe, Africa, South America, Oceania, and the Middle East. Most fatalities occurred in North America (the United States) and Asia (China and Singapore). Engineered recombinant adenoviruses have played a crucial role as vaccine vectors. In this study, we constructed a recombinant adenovirus, Ad4ITRmut-Ad7E3, and evaluated it in vitro and in vivo. We observed that the replication rate of Ad4ITRmut-Ad7E3 was lower than that of the RI-67 strain, indicating that the mutation of inverted terminal repeats (ITRs) weakened the replication ability of HAdV4. Immunization of BALB/c mice with the bivalent Ad4ITRmut-Ad7E3 vaccine strain, administered by intraperitoneal injection and oral gavage, resulted in the elicitation of neutralizing antibodies targeting HAdV4 and HAdV7. This finding not only provides a novel method and technique for the efficient construction of a polyvalent recombinant adenovirus vaccine candidate against HAdV4 and HAdV7 but also against other prevalent adenovirus serotypes such as HAdV3, HAdV11, HAdV14, and HAdV55, from various regions.

The emerging viruses within the genus Henipavirus in the family Paramyxoviridae pose a great threat to public biosafety. To develop a quadruple real-time fluorescence-based quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay is pivotal for the early warning of the potential of zoonotic infectious diseases. Specific primers and probes were designed for the relatively conserved regions based on whole genome sequences of Langya virus (LayV), Mojiang virus (MojV), Nipah virus (NiV), and Cedar virus (CedV), followed by the establishment of a quadruple real-time fluorescence-based qRT-PCR detection method. No cross-reactivity was observed with other viral nucleic acids. The optimal linear detection range for LayV, MojV, NiV, and CedV was 10¹-10⁸ copies/μL, and the lower limit of detection was 10 copies/μL. Three different DNA concentrations of LayV, MojV, NiV, and CedV (10⁴, 10⁵, and 10⁶ copies/μL) were tested 14 times, achieving good repeatability. The standard deviation of the cycle threshold values for each concentration was <0.5 and the coefficient of variation was <3 %. Furthermore, the amplification efficiency of quadruple real-time fluorescence-based qRT-PCR was >90 %, and the correlation coefficient was >0.99. The established quadruple real-time fluorescence-based qRT-PCR assay for the detection of LayV, MojV, NiV, and CedV exhibits good sensitivity, specificity, and repeatability. Therefore, it can be used to detect Henipavirus and other related clinical specimens.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has severely impacted public health. In 2022, the Omicron variant of SARS-CoV-2 rapidly became the dominant circulating variant in the local COVID-19 outbreaks in Tianjin Municipality, China. To gain a deeper understanding of the genetic variations of the Omicron variant in Tianjin, specimens from individuals who tested positive for SARS-CoV-2 between December 2021 and November 2022 were used for virus whole genome sequencing and phylogenetic analysis. A total of 1,674 high-quality Omicron sequences were obtained, consisting of 1,339 sequences from local cases belonging to 20 Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages and 335 sequences from imported cases belonging to 70 lineages. Tianjin experienced five waves of local outbreaks, accompanied by multiple substitutions among subvariants, ranging from the initial BA.1.1 lineage to the subsequent BA.2, BF.7, and BA.5.2 lineages. The evolutionary rate of local strains, estimated to be 28.999 substitutions per year, and the evolutionary rate of imported strains, estimated to be 24.946 substitutions per year, were lower than that of the strains circulating globally. The additional substitutions and deletions of local strains have been used to identify and disrupt the virus transmission chains. The subvariants such as BA.5.2.48, BA.5.2.49, BF.7.14, and XBB.1 circulating in the fifth epidemic wave presented criterial immune escape mutations including S: R346T, S: L452R and S: F486V. It is essential to implement genomic surveillance strategies to investigate further the development of genomic mutation characteristics in the SARS-CoV-2 variant. This ongoing monitoring will contribute to a better understanding of the virus's genetic changes and aid in effective control measures.

The rapid spread of mobile tigecycline resistance presents a significant public health threat, particularly with the increasing prevalence of tet(X4)-positive Enterobacterales across various species. This study aimed to investigate the epidemic features and transmission dynamics of tet(X4)-positive Klebsiella pneumoniae (K. pneumoniae) through the analysis of 206 raw meats, including pork (n = 182), beef (n = 16), duck (n = 5), and chicken (n = 3). These samples were collected from schools, markets, and restaurants in Chengdu City, China. A total of 25 isolates were obtained from 13 administrative regions. All isolates exhibited resistance to tetracycline, tigecycline, ampicillin, chloramphenicol, and florfenicol. Over half of the isolates also demonstrated resistance to streptomycin (80 %), sulfamethoxazole/trimethoprim (72 %), ciprofloxacin (64 %), and ampicillin/sulbactam (56 %). Among these strains, 14 distinct sequence types (STs) were identified, revealing evidence of inter-regional clonal spread, notably among 9 K. pneumoniae ST3393. Phylogenetic analysis revealed the presence of two K. pneumoniae ST5 closely resembling hypervirulent K. pneumoniae from Jiangsu. Importantly, 12 isolates were capable of transferring tigecycline resistance to Escherichia coli J53. Further plasmid analysis showed that the tet(X4)-harboring plasmids in K. pneumoniae could be classified into four types, primarily belonging to the IncFIA(HI1)/HI1A/HI1B hybrid plasmid (n = 16) and IncFII plasmid (n = 7), which significantly contributed to the cross-species dissemination of tet(X4). In summary, this study highlights the prevalence of MDR tet(X4)-positive K. pneumoniae in Chengdu, driven predominantly by clonal expansion and plasmid-mediated horizontal gene transfer. These findings emphasize the importance of continuous surveillance of tet(X4)-positive K. pneumoniae in raw meat and the implementation of effective measures to control their spread.

Antibiotic resistance is an escalating global concern, leading to millions of annual fatalities. Antibiotic resistance genes (ARGs) present in bacteria equip them to withstand the effects of antibiotics. Intra- and interspecific ARGs transmission through horizontal gene transfer further exacerbates resistance dissemination. The presence of ARGs in the environment heightens the probability of human exposure via direct inhalation, ingestion, or contact with polluted air, food, or water, posing substantial biosafety and health hazards. Consequently, ARGs represent a critical focal point in public health and environmental safety and are classified as emerging contaminants. This perspective underscores the necessity to assess ARG exposure within the One Health framework and to accord greater attention to the mitigation strategies and tactics associated with ARGs.

Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) are widespread in China, with occurrences documented in humans, animals, and the environment. The dissemination of ESBL-producing E. coli is likely facilitated by the widespread use of antibiotics in human and animal agriculture, the presence of antibiotic-resistant bacteria (ARBs) in animal feces, and close human-animal interactions. Plasmids, particularly those belonging to incompatibility (Inc) group, such as IncF, IncI, and IncH families, play a vital role in facilitating the horizontal gene transfer of ESBL genes across various sectors, from humans to animals and the environment. IS26 and IS1 elements also significantly influences the mobilization and evolution of antibiotic-resistance genes (ARGs), contributing to the spread of ESBL-producing E. coli. bla_CTX-M−14, bla_CTX-15, and bla_CTX-M−55 are prevalent in ESBL-producing E. coli across the three domains and are often found in conjunction with other ARGs. Considering these challenges, it is imperative to take proactive measures to prevent the further spread of ARBs. This includes the judicious and responsible use of antibiotics and efforts to minimize contact with animal feces. Sector-specific strategies should be developed to effectively educate and engage relevant personnel in tackling this multifaceted problem. These efforts are vital to combat the dissemination of ESBL-producing E. coli and preserve public health.

Monkeypox (mpox) outbreak in 2022 has caused more than 91,000 cases, has spread to 115 countries, regions, and territories, and has thus attracted much attention. The stability of poxvirus particles in the environment is recognized as an important factor in determining their transmission. However, few studies have investigated the persistence of poxviruses on material surfaces under various environmental conditions, and their sensitivity to biocides. Here, we systematically measured the stability of vaccinia virus (VACV) under different environmental conditions and sensitivity to inactivation methods via plaque assay, quantitative real-time polymerase chain reaction (qPCR), and Gaussia luciferase (G-luciferase) reporter system. The results show that VACV is stable on the surface of stainless steel, glass, clothing, plastic, towel, A4 paper, and tissue and persists much longer at 4 °C and −20 °C, but is effectively inactivated by ultraviolet (UV) irradiation, heat treatment, and chemical reagents. Our study raises the awareness of long persistence of poxviruses in the environment and provides a simple solution to inactivate poxviruses using common disinfectants, which is expected to help the control and prevention of mpox virus and future poxvirus outbreaks.

Coxsackievirus A6 of the D3a genotype (CVA6 D3a) is a primary pathogen causingmainland of China's hand, foot, and mouth disease (HFMD). Viral-like particle (VLP) vaccines represent a potential candidate vaccine to prevent HFMD. This study collected Anti-CVA6 D3a VLPs serum from BALB/c female mice immunized using CVA6 D3a VLPs. The neutralizing antibody levels were compared against the representative 14-JX2018 (D3a) and N4-YN2015 (D3b) strains between the antisera of different immune pathways. The immunoprotective effect of anti-CVA6 D3a VLPs against these strains was monitored using pathological sections and immunohistochemical results of lung and skeletal muscle tissues in seven-day-old Institute of Cancer Research (ICR) mice. Immunological protection against different branches of viruses was evaluated in 7-day-old (serum passive immune protection) and 14-day-old (VLPs active immune protection) neonatal ICR mice models. Serum-neutralizing antibody levels were positively correlated with the number of immunizations and higher against 14-JX2018 than against N4-YN2015. Furthermore, these levels were significantly higher with abdominal injection than intramuscular injection. The immunized serum of 7-day-old ICR mice inoculated three times was 100 % protected against CVA6 D3a 14-JX2018 (lethal titer: 10^6.25 TCID₅₀) and CVA6 D3b N4-YN2015 (lethal titer: 10^5.25TCID₅₀) fatal attacks, respectively. For ICR mice that have completed two active immunizations for 14 days, both CVA6 D3a 14-JX2015 (challenge titer: 10^8.25 TCID₅₀) and CVA6 D3b N4-YN2015 (challenge titer: 10^7.25 TCID₅₀) were used for the challenge, and the mice were able to survive. Overall, the CVA6 D3a VLPs prepared in this study are a potential vaccine candidate for CVA6, as it has the optimal protective effect against both CVA6 D3a and D3b evolutionary branches viruses.