A5101743176- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- T-cell and B-cell Immunology
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Genetics and Biotechnology
- Immune Cell Function and Interaction
- RNA and protein synthesis mechanisms
- Mosquito-borne diseases and control
- Bacteriophages and microbial interactions
- Animal Virus Infections Studies
- Enzyme Production and Characterization
- Viral Infections and Outbreaks Research
- Cytomegalovirus and herpesvirus research
- Virus-based gene therapy research
- Bacillus and Francisella bacterial research
- CRISPR and Genetic Engineering
- Enzyme Structure and Function
- Genomics and Phylogenetic Studies
- Microbial infections and disease research
- Forensic and Genetic Research
- Animal Disease Management and Epidemiology
- Biochemical and Structural Characterization
- Machine Learning in Bioinformatics
- RNA Interference and Gene Delivery
- Microbial Inactivation Methods
University of Copenhagen
2010-2023
Novozymes (Denmark)
2002-2022
Max Planck Institute for Molecular Genetics
1990
University of California, Davis
1990
Abstract Background Bacillus licheniformis is a Gram-positive, spore-forming soil bacterium that used in the biotechnology industry to manufacture enzymes, antibiotics, biochemicals and consumer products. This species closely related well studied model organism subtilis , produces an assortment of extracellular enzymes may contribute nutrient cycling nature. Results We determined complete nucleotide sequence B. ATCC 14580 genome which comprises circular chromosome 4,222,336 base-pairs (bp)...
Abstract Binding of peptides to MHC class I (MHC-I) molecules is the most selective event in processing and presentation Ags CTL, insights into mechanisms that govern peptide–MHC-I binding should facilitate our understanding CTL biology. Peptide–MHC-I interactions have traditionally been quantified by strength interaction, is, affinity, yet it has shown stability complex a better correlate immunogenicity compared with affinity. In this study, we experimentally analyzed large panel human...
Efficient presentation of peptide‐ MHC class I (p ‐I) complexes to immune T cells should benefit from a stable ‐I interaction. However, it has been difficult distinguish stability other requirements for binding, example, affinity. We have recently established high‐throughput assay p stability. Here, we generated large database containing measurements complexes, and re‐examined previously reported unbiased analysis the relative contributions antigen processing in defining cytotoxic lymphocyte...
Summary Major histocompatibility complex class I ( MHC ‐I) molecules play an essential role in the cellular immune response, presenting peptides to cytotoxic T lymphocytes CTL s) allowing system scrutinize ongoing intracellular production of proteins. In early 1990s, immunogenicity and stability peptide– ‐I (pMHC‐I) were shown be correlated. At that time, measuring was cumbersome time consuming only small data sets analysed. Here, we investigate this fairly unexplored area on a large scale...
MHC class I molecules (HLA-I in humans) present peptides derived from endogenous proteins to CTLs. Whereas the peptide-binding specificities of HLA-A and -B have been studied extensively, little is known about HLA-C specificities. Combining a positional scanning combinatorial peptide library approach with peptide-HLA-I dissociation assay, this study we general strategy determine specificity any molecule. We applied novel 17 most common molecules, for 16 these successfully generated matrices...
Abstract The attenuated yellow fever (YF) vaccine (YF-17D) was developed in the 1930s, yet little is known about protective mechanisms underlying its efficiency. In this study, we analyzed relative contribution of cell-mediated and humoral immunity to vaccine-induced protection a murine model YF-17D infection. Using different strains knockout mice, found that CD4+ T cells, B Abs are required for full clinical vaccinated whereas CD8+ cells dispensable long-term survival after intracerebral...
PrsA is an extracytoplasmic folding catalyst essential in Bacillus subtilis. Overexpression of the native from B. subtilis has repeatedly lead to increased amylase yields. Nevertheless, little known about how overexpression heterologous PrsAs can affect secretion.In this study, final yield five extracellular alpha-amylases was by co-expression up 2.5 fold. The effect on alpha-amylase secretion specific co-expressed alpha-amylase. Co-expression a significantly reduce stress response....
Abstract Outbreaks of Yellow Fever occur regularly in endemic areas Africa and South America frequently leading to mass vaccination campaigns straining the availability attenuated vaccine, YF-17D. The WHO has recently decided discontinue regular booster-vaccinations since a single is deemed confer life-long immune protection. Here, we have examined humoral (neutralizing antibody) cellular (CD8 CD4 T cell) responses primary booster vaccinees (the latter spanning 8 36 years after vaccination)....
We have generated a panel of transgenic mice expressing HLA-A*01:03, -A*24:02, -B*08:01, -B*27:05, -B*35:01, -B*44:02, or -C*07:01 as chimeric monochain molecules (i.e., appropriate HLA α1α2 H chain domains fused with mouse α3 domain and covalently linked to human β2-microglobulin). Whereas surface expression several transgenes was markedly reduced in recipient that coexpressed endogenous H-2 class I molecules, substantial all observed lacking molecules. In these transgenic/H-2 null mice, we...
Human cytomegalovirus (HCMV) is an important human pathogen. It a leading cause of congenital infection and infectious threat to recipients solid organ transplants as well allogeneic hematopoietic cell transplants. Moreover, it has recently been suggested that HCMV may promote tumor development. Both CD4+ CD8+ T responses are for long-term control the virus, adoptive transfer HCMV-specific cells led protection from reactivation disease. Identification epitopes primarily focused on against...
The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) widely evaluated as recombinant vectors, particularly in the context prophylactic against viral infections which induction CD8+ T-cell mediated...
To facilitate the study of regulation rpsA gene, a translational fusion between gene and 1acZ was constructed. Synthesis protein repressed about lo-fold when supplied in trans on multicopy plasmid. This repression is similar to post-transcriptional previously found for wild type gene. Addition purified Sl coupled vitro transcription-translation system caused specific reduction synthesis rpsA-1acZ protein. various subdomain fragments showed that Nterminal fragment, possessing ribosome binding...
Examining CD8+ and CD4+ T cell responses after primary Yellow Fever vaccination in a cohort of 210 volunteers, we have identified tetramer-validated 92 50 epitopes, many inducing strong prevalent (i.e. immunodominant) responses. Restricted by 40 14 HLA-class I II allotypes, respectively, these wide population coverage might be considerable academic, diagnostic therapeutic interest. The broad epitopes HLA overcame the otherwise confounding effects diversity non-HLA background providing first...
The enzymatic digestion of starch by α-amylases is one the key biotechnological reactions recent times. In search for industrial biocatalysts, family GH13 α-amylase BHA from Bacillus halmapalus has been cloned and expressed. three-dimensional structure at 2.1 Å resolution determined in complex with (pseudo)tetrasaccharide inhibitor acarbose. Acarbose found bound as a nonasaccharide transglycosylation product spanning −6 to +3 subsites. Careful inspection electron density suggests that ligand...
Despite an abundance of peptides inside a cell, only small fraction is ultimately presented by HLA-I on the cell surface. The have allomorph-specific motifs and are restricted in length. So far, detailed length studies been limited to few allomorphs. Peptide-HLA-I (pHLA-I) complexes different allomorphs qualitatively quantitatively influenced tapasin degrees, but again, its effect has investigated for number Although both peptide dependence known be important presentation, relationship...
Immunotherapy has increased overall survival of metastatic cancer patients, and antigens are promising vaccine targets. To fulfill the promise, appropriate tailoring formulations to mount in vivo cytotoxic T cell (CTL) responses toward co-delivered is essential. Previous development therapeutic vaccines largely been based on studies mice, majority these candidate failed induce subsequent human clinical trials. Given that antigen dose volume pigs translatable humans porcine immunome closer...