A DNA Vaccine in Which the RSV-F Ectodomain Is Covalently Linked to the Burkholderia pseudomallei Antigens TssM and Hcp1 Augments the Humoral and Cytotoxic Response in Mice

DNA vaccines have great potential to control infectious disease, particularly those caused by intracellular organisms. They are inexpensive to produce and can be quickly modified to combat emerging infectious threats, but often fail to generate a strong immunologic response limiting enthusiasm for their use in humans and animals. To improve the immunogenic response, we developed a DNA vaccine in which the F protein ectodomain of Respiratory Syncytial Virus (RSV-F) was covalently linked to specific antigens of interest. The presence of the RSV-F ectodomain allowed secretion of the translated fusion product out of the originally transfected cells followed by its active binding to adjacent cells. This allowed the targeting of a greater number of cells than those originally transfected, enhancing both humoral and cytotoxic immune responses against the expressed antigen(s). We developed an engrafted mouse model that used antigen-expressing tumor cells to assess the in vivo cytotoxic immune response to specific antigens. We then used this model to demonstrate that a DNA vaccine in which the RSV-F ectodomain is fused to two antigens expressed by Burkholderia pseudomallei, the intracellular gram-negative organism that causes melioidosis, generated a stronger cytotoxic response than a DNA vaccine that lacked the RSV-F sequence while still generating a robust humoral response.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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Lipopolysaccharides (LPSs) of Gram-negative bacteria comprise lipid A, core, and O-polysaccharide (OPS) components. Studies have demonstrated that LPSs isolated from the pathogenic species Burkholderia pseudomallei and Burkholderia mallei and from less-pathogenic species, such as Burkholderia thailandensis, are potent immune stimulators. The LPS structure of B. pseudomallei, the causative agent of melioidosis, is highly conserved in isolates from Thailand; however, the LPSs isolated from other, related species have not been characterized to enable understanding of their immune recognition and antigenicities. Here, we descr...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research
Abstract Burkholderia lethal factor 1 (BLF1), a glutamine deamidase, is a key virulence factor that plays significant role in B. pseudomallei pathogenesis. To elucidate the BLF1 immunological responses, two truncated BLF1 structural units, BLF1-C (90-211 amino acids) with structural similarity to T. maritima Chemoreceptor glutamine deamidase (CheD) protein, and BLF1-N (1-89 amino acids) disparate to CheD were identified from the 23 kDa BLF1 protein. Both the components were devoid of toxicity in mice and elicited an antibody titer of 1:16,000 that reacted with the respective truncated proteins and BLF1. A549 cel...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
by Trung T. Trinh, Karoline Assig, Quyen T. L. Tran, Andr é Goehler, Linh N. H. Bui, Claudia Wiede, Bettina Folli, Sabine Lichtenegger, Tinh T. Nguyen, Gabriel E. Wagner, Christian Kohler, Ivo Steinmetz BackgroundIsolation of the soil bacteriumBurkholderia pseudomallei from tropical environments is important to generate a global risk map for man and animals to acquire the infectious disease melioidosis. There is increasing evidence, that the currently recommended soil culture protocol using threonine-basal salt solution with colistin (TBSS-C50) for enrichment ofB.pseudomallei and Ashdown agar for subsequent subcultu...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research
Microbial Drug Resistance, Ahead of Print.
Source: Microbial Drug Resistance - Category: Microbiology Authors: Source Type: research
CONCLUSION: Young boys were found to be more commonly affected by orbital cellulitis than young girls. Staphylococcus aureus was the most common isolated micro-organism. Methicillin-resistant Staphylococcus aureus and Burkholderia pseudomallei caused severe infection. Sinusitis and upper respiratory tract infection were the most common predisposing factors. A majority of the children improved with medical treatment alone. Our findings are in slight disagreement with other published reports on paediatric orbital cellulitis, especially from the Asian region. PMID: 31598730 [PubMed - as supplied by publisher]
Source: Singapore Medical Journal - Category: General Medicine Authors: Tags: Singapore Med J Source Type: research
This study enriches the inhibitory profiles database for γ-class CAs and promotes the identification of new potent and selective inhibitors against bacterial isoforms over human off-target ones. These agents are of remarkable interest and importance in the search of novel, worldwide required, antibiotic agents possessing alternative mechanisms of action as a strategy to overcome the spread to antimicrobic resistance. PMID: 31604186 [PubMed - as supplied by publisher]
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research
ConclusionsThe reduced growth speed and increased drug resistance of B. pseudomallei SCV strain may be related to those variations in genome, which provided some clues to their associations between the morphotypic and phenotypic characteristics of colony variants, and the potential associations of its colony morphotypes with metabolism, antibiotic resistance and virulence.
Source: Journal of Global Antimicrobial Resistance - Category: Infectious Diseases Source Type: research
We report the methylome sequencing and annotation of Burkholderia pseudomallei D286 based on high-throughput profiling using PacBio SMRT technology
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Burkholderia pseudomallei Source Type: research
Autotransporters, or type 5 secretion systems, are widespread surface proteins of Gram-negative bacteria often associated with virulence functions. Autotransporters consist of an outer membrane β-barrel domain and an exported passenger. In the poorly studied type 5d subclass, the passenger is a patatin-like lipase. The prototype of this secretion pathway is PlpD of Pseudomonas aeruginosa, an opportunistic human pathogen. The PlpD passenger is a homodimer with phospholipase A1 (PLA1) activity. Based on sequencing data, PlpD-like proteins are present in many bacterial species. We characterized the enzymatic activity, sp...
Source: Biochemical Journal - Category: Biochemistry Authors: Tags: Research Articles Source Type: research
Abstract Burkholderia pseudomallei (B. pseudomallei), the etiological agent of melioidosis, is a Gram-negative bacterium with additional concern as a biothreat pathogen. The mortality rate from B. pseudomallei varies depending on the type of infection and extent of available health care, but in the case of septicemia left untreated it can range from 50 - 90%. Current therapy for melioidosis is biphasic, consisting of parenteral acute-phase treatment for two weeks or longer, followed by oral eradication-phase treatment lasting several months. An effective oral therapeutic for outpatient treatment of acute-phase mel...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research
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