ng/ml sCD14 recombinant
3/ Conclusion générale
Nos travaux nous ont permis d’étudier plus en détail les propriétés et modes d’action de deux molécules synthétiques présentant la caractéristique commune d’être des ligands du récepteur TLR4. Cette étude amène de ce fait à une meilleure compréhension des mécanismes d’action de ligands TLR4 distincts et ceci de manière plus globale.
Premièrement, les liposomes de diCn-amidine pourraient activer le récepteur TLR4 en interagissant avec son site actif. Les propriétés physicochimiques des liposomes de diCu-amidine pourraient constituer un atout pour la formulation et son association avec d'autres composés.
-81-L'entreprise pharmaceutique utilise effectivement des liposomes dans la formulation de certains vaccins.
Deuxièmement, le CRX-527 présente quant à lui la particularité d'activer le TLR4 sans que le co-récepteur CD 14 ne soit nécessaire, un avantage pour faire face notamment à certaines déficiences en CD14. Cet agoniste pourrait également nous aider à discriminer les rôles des CD14, soluble et membranaire, comme le suggèrent nos expériences.
Le CRX-527 qui est un agoniste du TLR4 particulièrement puissant, stimule fortement les réponses immunes. Il a donc l'avantage de l'efficacité et le désavantage du risque d'induire des réponses trop fortes qui pourraient aboutir à une inflammation excessive, ou à la possibilité de rompre la tolérance immunologique, et d'induire de l'autoimmunité. À l'opposé, la diCn-amidine induit des réponses moins fortes qui pourraient s'avérer utiles dans certaines situations, comme dans le cas d'un vaccin pédiatrique.
Ces deux molécules peuvent être obtenues par synthèse chimique. Tout composé synthétique apporte généralement un plus en matière de biosécurité (absence de contaminant biologique plus facilement contrôlée). La diCn-amidine est particulièrement facile à produire, comparé à la synthèse du CRX-527 qui est plus complexe. Mais rappelons que la production de l'adjuvant MPL, qui est la molécule biologique parente du CRX-527, présente des aléas encore bien plus importants.
Globalement, les deux molécules que nous avons étudiées, pourraient être utiles au développement de nouveaux vaccins, ou comme outil de recherche sur les vaccins. Chacune aurait des cibles vaccinales distinctes, au vu de leurs nombreuses propriétés différentes discutées précédemment dans ce travail, avec leurs avantages et leurs faiblesses.
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