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type
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Thesis advisor
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Author
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alternative label
| - Approche génomique pour le développement de vaccins contre Haemophilus influenzae non encapsulée responsable de l'otite de l'oreille moyenne
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dc:subject
| - Fluorescence
- Biofilms
- Transcriptome
- Thèses et écrits académiques
- Microscopie
- Chinchilla laniger
- Infection in vivo
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preferred label
| - Genome-wide approach to vaccine target candidates identification against otitis media causing nontypeable Haemophilus influenzae
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Language
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Subject
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dc:title
| - Genome-wide approach to vaccine target candidates identification against otitis media causing nontypeable Haemophilus influenzae
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Degree granting institution
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note
| - WHILE A SUCCESSFUL CAPSULAR VACCINE HAS BEEN DEVELOPED FOR ENCAPSULATED SEROTYPE B HAEMOPHILUS INFLUENZAE (HI), NO VACCINE EXISTS FOR UNENCAPSULATED HI RESPONSIBLE FOR RESPIRATORY TRACT INFECTIONS. THESE INCLUDE OTITIS MEDIA THAT CAN RESULT IN SEQUELAE IN 20% OF CASES AND REMAINS A PRIMARY REASON FOR PEDIATRICIAN VISITS IN DEVELOPED COUNTRIES. THE GOAL OF THIS STUDY WAS TO DEVELOP A SYSTEM TO ANALYZE HI GENES EXPRESSION GENOME-WIDE DURING THE DIFFERENT STAGES OF DISEASE. SUCCESSFUL COMPREHENSIVE ANALYSIS AT THIS LEVEL WOULD PROVIDE CRITICAL INSIGHT INTO THE PATHOGENESIS OF NTHI DURING THE COURSE OF OTITIS MEDIA AS WELL AS IN VIVO EXPRESSION OF PARTICULAR SURFACE ANTIGENS AND THUS POTENTIAL CANDIDATE VACCINE TARGETS ASSOCIATED WITH INFECTION. AN INITIAL SCREEN OF ALL PUBLICLY AVAILABLE NTHI GENES WAS CARRIED OUT AND CONSERVED SEQUENCES THEN REFERENCED IN A DATABASE: CALLED THE HI GENOMIC MASTER KEY DATABASE. THIS DATABASE ALLOWS FOR SUBSEQUENT SCREENING OF VACCINE TARGET CANDIDATES IN ANY NTHI ISOLATE OF UNKNOWN GENOMIC SEQUENCE. ALL RNA PROCEDURES AND PROTOCOLS NEEDED FOR GENE EXPRESSION ANALYSES WERE DEVELOPED AND ADAPTED TO THE SPECIFIC EXPERIMENTAL CONDITIONS OF THIS STUDY. ADDITIONALLY, THE NOVEL MULTIPLE CONSECUTIVE LAVAGE SAMPLING METHODOLOGY WAS DEVELOPED TO INCREASE THE AMOUNT OF EX VIVO BACTERIAL MRNA AVAILABLE FOR MICROARRAY ANALYSIS. THIS SAMPLING METHOD ALSO PROVIDED INSIGHTS INTO NTHI INDUCED OTITIS MEDIA WITH RESULTING CLINICAL IMPLICATIONS. FINALLY, MICROARRAY EX VIVO GENE EXPRESSION ANALYSES WERE USED HERE FOR THE FIRST TIME TO STUDY NTHI IN VIVO TRANSCRIPTIONAL PROFILE GENOME-WIDE DURING THE COURSE OF NASOPHARYNGEAL COLONIZATION AND MIDDLE EAR INFECTION.
- BIEN QU’IL EXISTE UN VACCIN CONTRE HAEMOPHILUS INFLUENZAE (HI) TYPE B, AUCUN N’EST DISPONIBLE CONTRE LA FORME NON ENCAPSULEE (NTHI) RESPONSABLE D'INFECTIONS DU SYSTEME RESPIRATOIRE TELLE QUE L'OTITE DE L'OREILLE MOYENNE. CETTE INFECTION ENTRAINE DES SEQUELLES AUDITIVES DANS 20% DES CAS ET RESTE LA PREMIERE CAUSE DE VISITE PEDIATRIQUE DANS LES PAYS DEVELOPPES. L’ENJEU DE CE TRAVAIL A ETE DE DEVELOPPER UN SYSTEME PERMETTANT L'ANALYSE DE L'EXPRESSION GENOMIQUE DURANT LES PHASES DE L'INFECTION. ET CE DANS LE BUT D’ACQUERIR UNE MEILLEURE COMPREHENSION DE LA PATHOGENESE DE NTHI ET D’IDENTIFIER LES ANTIGENES DE SURFACE TRANSCRITS IN VIVO, REPRESENTANT DES CIBLES POTENTIELLES POUR UN VACCIN. LES SEQUENCES DES GENES DE HI ONT ETE ANALYSEES POUR DETERMINER LES DOMAINES CONSERVES, ET REPERTORIES DANS UNE BANQUE DE DONNEES: \"THE HI GENOMIC MASTER KEY\". CELLE-CI PERMET LA CONSTRUCTION D’AMORCES ET SONDES POUR L’ETUDE DE CES GENES DANS DES SOUCHES DE SEQUENCES INCONNUES. LES PROTOCOLES NECESSAIRES A LA MANIPULATION, L’ISOLATION ET LA PURIFICATION D’ARN ONT ETE MIS EN PLACE ET ADAPTES AUX CONDITIONS EXPERIMENTALES. UNE NOUVELLE METHODE D’ACQUISITION D’ECHANTILLONS EX VIVO DANS LE CHINCHILLA A ETE DEVELOPPEE AFIN D’AUGMENTER LA QUANTITE DE BACTERIES DISPONIBLES POUR L’ANALYSE MICROARRAY. L’AFFINEMENT DES CONNAISSANCES DES MECANISMES INFECTIEUX DE NTHI, PAR CETTE NOUVELLE METHODE, A DES RETOMBEES CLINIQUES POUR LES TRAITEMENTS ANTIBIOTIQUES ET LE DEVELOPPEMENT DE VACCINS. LA PLATEFORME MICROARRAY POUR L’ETUDE DU TRANSCRIPTOME IN VIVO A ETE ETABLIE ET A PERMIS POUR LA PREMIERE FOIS L’ETUDE IN VIVO DU TRANSCRIPTOME AU COURS DES PHASES DE COLONISATION ET D’INFECTION D’UN PATHOGENE.
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dc:type
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http://iflastandar...bd/elements/P1001
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rdaw:P10219
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has content type
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is primary topic
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is rdam:P30135
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