Emory University

Other

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Florida State University Research Foundation, Inc.

David S Stephens

Susu Zughaier

Yih-Ling Tzeng

Ritu Aneja

Anup K Datta

Russell W Carlson

John S Swartley

Frederick Quinn

Shanta Zimmer

Kathryn Gay

Efrain M Ribot

Nigel Raymond

Seshu K Gudlavalleti

Charlene Marree Kahler

The invention relates to the innate immune pathway and anti-inflammatory molecules with therapeutic properties. In some embodiments, the invention relates to compounds and pharmaceutical compositions and methods of using the compounds and compositions to treat inflammatory diseases including inflammation associated with auto-immune diseases.

Noscapine and analogs and methods related thereto

Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup Ausing the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

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Provided herein are mutant strains ofwhich produce Kdo-free lipid A as well as the Kdo-free lipid A molecules and immunogenic compositions containing such Kdo-free lipid A molecules from astrain containing a genetically stable mutation which inactivates a gene selected from the group consisting of genes encoding arabinose-5-phosphate isomerase, CMP-Kdo synthetase and CMP-Kdo transferase.NMB206 is a specifically exemplified strain which harbors a stable insertion mutation in the gene (kpsF) encoding A5P isomerase; strain NMB-249 is a specifically exemplified strain with a stable insertion mutation in the gene (kdtA) encoding CMP-Kdo synthetase, and strain NMB259 is specifically exemplified strain with a stable insertion mutation in the gene (kdsB) encoding CMP-Kdo transferase. Also provided by the present invention are methods for the production of Lipid A flee of 3-keto-3-deoxyoctanoic acid using these genetically stablemutants. Also describes is pYT250, a plasmid functional in neisseriae and in enterics such as

Neisseria mutants, lipooligosaccharides and immunogenic compositions

Macrolide resistance associated with macrolide efflux (mef) inhas been defined with respect to the genetic structure and dissemination of a novel mefE-containing chromosomal insertion element. The mefE gene is found on the 5'-end of a 5.5 kb or 5.4 kb insertion designated mega (acrolideffluxeneticssembly) found in at least four distinct sites of the pneumococcal genome. The element is transformable and confers macrolide resistance to susceptible. The first two open reading frames (ORFs) of the element form an operon composed of mefE and a predicted ATP-binding cassette homologous to msrA. Convergent to this efflux operon are three ORFs with homology to stress response genes of Tn5252. Mega is related to mefA-containing element Tn1207.1. Macrolide resistance due to mega has been rapidly increased by clonal expansion of bacteria containing it and horizontally by transformation of previously sensitive bacteria.

Macrolide efflux genetic assembly

Genes isolated from , as well as isolated nucleic acids, probes, expression cassettes, polypeptides, antibodies, immunogenic compositions, antisense nucleic acids, amplification mixtures, and new invasion deficient swains of are provided Methods of detecting and nucleic acids, and methods of inhibiting the invasion of mammalian cells by are also provided.

Invasion associated genes from Neisseria meningitidis serogroup B

The present invention is based on the discovery of meningococcal isolates having genetic markers of a particular serogroup but expressing a capsular polysaccharide of a different serogroup. These isolates and prototype serogroup A, B, C, Y and W-135 strains were used to define the capsular biosynthetic operon of the major meningococcal serogroups and to show that capsule switching occurs as a result of allelic exchange of, for example, the polysialyl-transferase gene. Findings of capsule switching in vivo indicate that closely related virulent meningococcal clones may not be recognized by traditional serogroup-based surveillance and can escape vaccine-induced or natural protective immunity by capsule switching. The invention provides recombinant meningococcal strains, recombinant DNA constructs and immunological preparations useful as diagnostic probes for detection and diagnosis of meningococcal diseases, screening for specific meningococcal serogroups and broad based immunizations with multivalent capsular polysaccharide conjugate vaccines.

Serogroup-specific nucleotide sequences in the molecular typing of bacterial isolates and the preparation of vaccines thereto

Provided herein are mutant strains of Neisseria meningitidis which produce lipooligosaccharide (LOS) differing from the wild-type LOS in structure as well as the mutant LOS molecules and immunogenic compositions containing truncated LOS molecules from a Neisseria strain containing a genetically stable in a gene selected from the group consisting of genes encoding .alpha.-1,2-N-acetylglucosamine transferase and a gene homology to an Escherichia coli gene encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase. N. meningitidis NMB-559 harbors an insertion mutation in the gene encoding .alpha.-1, 2-N-acetylglucosamine transferase, and N. meningitidis NMB-469 harbors an insertion mutation in an nlaB gene, the protein product of which has significant amino acid sequence homology to the E. coli gene encoding 1-acyl-sn-glycerol-3-phosphate acyltransferase.

Growing community of inventors

Stone Mountain, GA, United States of America

David S Stephens