Vaccination with a trivalent Klebsiella pneumoniae vaccine confers protection in a murine model of pneumonia.

Klebsiella pneumoniae (K. pneumoniae) is an opportunistic pathogen and the major cause of healthcare-associated infections, which are increasingly complicated by the prevalence of highly invasive and hyper-virulent K. pneumoniae strains, necessitating the development of alternative strategies for combatting infections caused by this bacterium.

A highly neutralizing human monoclonal antibody targeting a novel linear epitope on staphylococcal enterotoxin B.

Staphylococcal Enterotoxin B (SEB), produced by (), is a powerful superantigen that induces severe immune disruption and toxic shock syndrome (TSS) upon binding to MHC-II and TCR. Despite its significant impact on the pathogenesis of , there are currently no specific therapeutic interventions available to counteract the mechanism of action exerted by this toxin. In this study, we have identified a human monoclonal antibody, named Hm0487, that specifically targets SEB by single-cell sequencing using PBMCs isolated from volunteers enrolled in a phase I clinical trial of the five-antigen vaccine.

A rational designed multi-epitope vaccine elicited robust protective efficacy against Klebsiella pneumoniae lung infection.

Background: The emergence of drug-resistant strains of Klebsiella pneumoniae (K. pneumoniae) has become a significant challenge in the field of infectious diseases, posing an urgent need for the development of highly protective vaccines against this pathogen.

Methods And Results: In this study, we identified three immunogenic extracellular loops based on the structure of five candidate antigens using sera from K.

PM induce lifespan reduction, insulin/IGF-1 signaling pathway disruption and lipid metabolism disorder in .

Introduction: Exposure to fine particulate matter (PM), especially PM, can induce various adverse health effects in populations, including diseases and premature death, but the mechanism of its toxicity is largely unknown.

Methods: Water-soluble components of PM (WS-PM) were collected in the north of China in winter, and combined in two groups with the final concentrations of 94 μg/mL (C group, AQI ≤ 100) and 119 μg/mL (C group, 100 < AQI ≤ 200), respectively. The acute and long-term toxic effects of WS-PM samples were evaluated in several aspects such as development, lifespan, healthspan (locomotion behavior, heat stress tolerance, lipofucin).

A repeated dose 28-day oral toxicity study of sodium dehydroacetate (DHA-S) in Wistar rats.

Sodium dehydroacetate (DHA-S) is a food additive and preservative. The present study was conducted to investigate the potential toxicity of repeated oral doses of DHA-S. DHA-S was administered orally by gavage to Wistar rats at doses of 0, 50, 100, or 200 mg/kg BW/day for 28 days, after which growth indicators, clinical pathology, organ weights, and histopathology were determined.

Host Immune Response to Clinical Hypervirulent Pulmonary Infections via Transcriptome Analysis.

(), especially those with hypervirulence, is becoming a global concern and posing great threat to human health. Studies on individual immune cells or cytokines have partially revealed the function of the host immune defense against pulmonary infection. However, systematic immune response against has not been fully elucidated.

Extracellular fibrinogen-binding protein released by intracellular Staphylococcus aureus suppresses host immunity by targeting TRAF3.

Many pathogens secrete effectors to hijack intracellular signaling regulators in host immune cells to promote pathogenesis. However, the pathogenesis of Staphylococcus aureus secretory effectors within host cells is unclear. Here, we report that Staphylococcus aureus secretes extracellular fibrinogen-binding protein (Efb) into the cytoplasm of macrophages to suppress host immunity.

A "Plug-and-Display" Nanoparticle Vaccine Platform Based on Outer Membrane Vesicles Displaying SARS-CoV-2 Receptor-binding Domain.

Biomimetic nanoparticles obtained from bacteria or viruses have attracted substantial interest in vaccine research and development. Outer membrane vesicles (OMVs) are mainly secreted by gram-negative bacteria during average growth, with a nano-sized diameter and self-adjuvant activity, which may be ideal for vaccine delivery. OMVs have functioned as a multifaceted delivery system for proteins, nucleic acids, and small molecules.

Effects of lanthanum nitrate on behavioral disorder, neuronal damage and gene expression in different developmental stages of Caenorhabditis elegans.

Rare earth elements (REEs) are widely used in the industry, agriculture, biomedicine, aerospace, etc, and have been shown to pose toxic effects on animals, as such, studies focusing on their biomedical properties are gaining wide attention. However, environmental and population health risks of REEs are still not very clear. Also, the REEs damage to the nervous system and related molecular mechanisms needs further research.

α-Hemolysin-Aided Oligomerization of the Spike Protein RBD Resulted in Improved Immunogenicity and Neutralization Against SARS-CoV-2 Variants.

The increase in confirmed COVID-19 cases and SARS-CoV-2 variants calls for the development of safe and broad cross-protective vaccines. The RBD of the spike protein was considered to be a safe and effective candidate antigen. However, the low immunogenicity limited its application in vaccine development.

Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-Resistant Infection.

Purpose: We previously reported that monoclonal antibody (mAb) cocktail improves survival in infection. In this study, we used acute pneumonia model and lethal sepsis model to investigate the efficacy of antibiotic combined with epitope-specific mAb cocktail in treating MRSA252 infection.

Methods: MRSA252 was challenged by tail vein injection or tracheal intubation to establish sepsis model or pneumonia model.

Pore-forming alpha-hemolysin efficiently improves the immunogenicity and protective efficacy of protein antigens.

Highly immunogenic exotoxins are used as carrier proteins because they efficiently improve the immunogenicity of polysaccharides. However, their efficiency with protein antigens remains unclear. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus to form a HlaH35A-PA0833 fusion protein (HPF).

Immunodominance of Epitopes and Protective Efficacy of HI Antigen Are Differentially Altered Using Different Adjuvants in a Mouse Model of Bacteremia.

HI, a fusion protein that consists of the alpha-toxin (Hla) and the N2 domain of iron surface determinant B (IsdB), is one of the antigens in the previously reported vaccine rFSAV and has already entered phase II clinical trials. Previous studies revealed that HI is highly immunogenic in both mice and healthy volunteers, and the humoral immune response plays key roles in HI-mediated protection. In this study, we further investigated the protective efficacy of immunization with HI plus four different adjuvants in a mouse bacteremia model.

Comet Assay Evaluation of Lanthanum Nitrate DNA Damage in C57-ras Transgenic Mice.

Due to the wide application of rare-earth elements (REEs) in the last decades, lanthanum has increasingly entered the environment and has gradually accumulated in the human body through the food chain. Lanthanum is worth paying attention in terms of food safety. Although the genotoxicity of lanthanum has been studied in vitro, data on its DNA damage in vivo rodent are limited, moreover, which have also presented some controversy.

Genome Sequence of Klebsiella pneumoniae YBQ, a Clinical Strain Isolated from the Sputum of a Patient with Severe Pneumonia.

We report here the genome of YBQ, a clinical strain isolated from the sputum of a patient with acute infection. The genome consists of a 5,119,471-bp circular chromosome and a 184,347-bp plasmid. Genome annotation predicted 5,028 coding DNA sequences (CDSs), 84 tRNAs, 25 rRNAs, and 47 small RNAs (sRNAs).

Innate Immune Effectors Play Essential Roles in Acute Respiratory Infection Caused by .

Innate immune effectors constitute the first line of host defense against pathogens. However, the roles of these effectors are not clearly defined during () respiratory infection. In the current study, we established an acute pneumonia model of respiratory infection in mice and confirmed that the injury was most severe 48 h post infection.

Comprehensive Analysis of SiNPs on the Genome-Wide Transcriptional Changes in .

Background: Large-scale production and application of amorphous silica nanoparticles (SiNPs) have enhanced the risk of human exposure to SiNPs. However, the toxic effects and the underlying biological mechanisms of SiNPs on remain largely unclear.

Purpose: This study was to investigate the genome-wide transcriptional alteration of SiNPs on .

Oligomerization of IC43 resulted in improved immunogenicity and protective efficacy against Pseudomonas aeruginosa lung infection.

IC43, a truncate form of outer membrane proteins OprF and OprI from Pseudomonas aeruginosa, is a promising candidate antigen and exists as monomer in solution. In this study, we generated the heptamer of IC43 by carrier protein aided oligomerization, which was confirmed by gel-filtration and chemical cross-linking analysis. The carrier protein naturally exists as a homo-heptamer, and IC43 was displayed on the surface of the carrier protein in the fusion protein.

Rapid and Broad Immune Efficacy of a Recombinant Five-Antigen Vaccine against Infection in Animal Models.

() is a leading cause of both healthcare-and community-associated infections globally, which result in severe disease and readily developing antibiotic resistance. Developing an efficacious vaccine against is urgently required. In the present study, we selected five conserved antigens, including the secreted factors α-hemolysin (Hla), staphylococcal enterotoxin B (SEB) and the three surface proteins staphylococcal protein A (SpA), iron surface determinant B N2 domain (IsdB-N2) and manganese transport protein C (MntC).

Design, implementation, and outcomes of an elective course on preliminary structural biology for undergraduate students majoring in biotechnology.

Biotechnological pharmaceuticals is a key course offered to third-year undergraduates majoring in biotechnology in our university. However, students often experience difficulties in understanding the principles of related technologies. In this study, we developed and implemented an elective course on preliminary structural biology for biotechnology undergraduates, aiming at reinforcing the principles of these technologies by experimental practice.

DNA vaccine encoding OmpA and Pal from Acinetobacter baumannii efficiently protects mice against pulmonary infection.

Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen that causes serious infections in the lungs, blood, and brain in critically ill hospital patients, resulting in considerable mortality rates every year. Due to the rapid appearance of multi-drug resistance or even pan-drug resistance isolates, it is becoming more and more difficult to cure A.

A High-throughput Assay for the Prediction of Chemical Toxicity by Automated Phenotypic Profiling of Caenorhabditis elegans.

Applying toxicity testing of chemicals in higher order organisms, such as mice or rats, is time-consuming and expensive, due to their long lifespan and maintenance issues. On the contrary, the nematode Caenorhabditis elegans (C. elegans) has advantages to make it an ideal choice for toxicity testing: a short lifespan, easy cultivation, and efficient reproduction.

PA0833 Is an OmpA C-Like Protein That Confers Protection Against Infection.

is a formidable pathogen that causes infections with high mortality rates. Because of its ability to form biofilms and rapidly acquire resistance to many first-line antibiotics, -related infections are typically difficult to cure by traditional antibiotic treatment regimes. Thus, new strategies to prevent and treat such infections are urgently required.

Classification and prediction of toxicity of chemicals using an automated phenotypic profiling of Caenorhabditis elegans.

Background: Traditional toxicological studies have relied heavily on various animal models to understand the effect of various compounds in a biological context. Considering the great cost, complexity and time involved in experiments using higher order organisms. Researchers have been exploring alternative models that avoid these disadvantages.

Immunodominant antigens that induce Th1 and Th17 responses protect mice against infection.

has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against in the stomach mucosa.