Meningococcal Factor H Binding Proteins in Epidemic Strains from Africa: Implications for Vaccine Development

Epidemics of meningococcal meningitis are common in sub-Saharan Africa. Most are caused by encapsulated serogroup A strains, which rarely cause disease in industrialized countries. A serogroup A polysaccharide protein conjugate vaccine recently was introduced in some countries in sub-Saharan Africa. The antibodies induced, however, may allow replacement of serogroup A strains with serogroup W-135 or X strains, which also cause epidemics in this region. Protein antigens, such as factor H binding protein (fHbp), are promising for prevention of meningococcal serogroup B disease. These proteins also are present in strains with other capsular serogroups. Here we report investigation of the potential of fHbp vaccines for prevention of disease caused by serogroup A, W-135 and X strains from Africa. Four fHbp amino acid sequence variants accounted for 81% of the 106 African isolates studied. While there was little cross-protective activity by antibodies elicited in mice by recombinant fHbp vaccines from each of the four sequence variants, a prototype native outer membrane vesicle (NOMV) vaccine from a mutant with over-expressed fHbp elicited antibodies with broad protective activity. A NOMV vaccine has the potential to supplement coverage by the group A conjugate vaccine and help prevent emergence of disease caused by non-serogroup A strains

Vers la synthèse totale de l'amphidinol 3 (ontrôle de la stéréoséquence C20-C27)

Les amphidinols sont une nouvelle classe de molécules naturelles de type polycétide dont l amphidinol-3 est la seule molécule possédant sa structure entièrement établie. L amphidinol-3 exhibe les meilleures activités biologiques de cette famille, principalement antifongique ethémolytique. La synthèse du fragment C17-C30 a été le premier objectif de ces travaux de thèse. Cette synthèse est basée sur l utilisation du para-tolylsulfoxyde comme auxiliaire de chiralité et d un bromoallylsilane comme corps central. Tous les centres asymétriques sont contrôlés avec de très hauts rapports diastéréomériques à l exception de la configuration du méthyle en C23. La non-maîtrise de ce centre, ainsi que des difficultés probables de couplage nous ont obligés à repenser notre stratégie. Suite au changement rétrosynthétique, la synthèse du fragment C13-C29 a été réalisée. L étape clef de cette voie synthétique est alors le couplage entre l anion lithié d un dérivé de 1,3-dithiane avec un aldéhyde a-branché. Après de nombreux ajustements de groupements protecteurs, le fragment C13-C29 est obtenu avec tous ses centres asymétriques maîtrisés.Amphidinols are a new class of polyketide extracted from dinoflagellates and exhib promising biological activities, such as antifungal and hemolytic. The amphidinol-3 is the only amphidinol possessing its fully elucidated structure and is the most biologically potent.The C17-C30 fragment is the first goal of our research. The synthesis is based on sulfoxide as chiral auxiliary and on a bromoallylsilane as bifunctionnal central core. All stereogenic centers are fully controlled with high diastereomeric ratios except the one bearing a methyl in C23 position. The lack of selectivity during the hydrogenation affording the C23 stereogenic center and plausible failures of fragment couplings force us to explore a new retrosynthesis. Our second goal is the synthesis of C13-C29 fragment. The new strategy is based on a coupling between a 1,3-dithiane derivative and an a-branched aldehyde. After protecting group optimization, the C13-C29 fragment is synthetized with all its stereogenic centers fully controlled.STRASBOURG-Bib.electronique 063 (674829902) / SudocSudocFranceF

Aryl Fluoroalkyl Sulfoxides: Optical Stability and p K a Measurement

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Nusbiarylins, a new class of antimicrobial agents : rational design of bacterial transcription inhibitors targeting the interaction between the NusB and NusE proteins

202105 bcvcAccepted ManuscriptRGCOthersRGC: 25100017Others: P0020297, P0000161Publishe

Design, synthesis and biological evaluation of antimicrobial diarylimine and –amine compounds targeting the interaction between the bacterial NusB and NusE proteins

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Interglaciaires pléistocènes en domaine karstique méditerranéen. Interprétation de la sédimentation et de la biodiversité fossile à la Caune de l’Arago (Tautavel, Pyrénées-Orientales)

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