− この都医学研セミナーは終了しました。 −
|演者||兼清優 Vaccine Research Center Staff Scientist|
|世話人||小原 道法 研究員 （感染制御プロジェクトリーダー）|
Recent advances in structural biology and nanotechnology creates opportunities to design immunogens with atomic-level precision. This synthetic approach enables the creation of unique vaccine immunogens that do not exist in nature, in particular, immunogens that are multimerized on protein scaffolds. These immunogens include designs based on biological macromolecules such as cargo proteins, multimeric enzymes, subviral particles and synthetic self-assembling proteins. Antigens presented in a rigidly multivalent array are known to be exceptionally immunogenic as they mimic the antigen display seen on bona fide viruses. This can induce a pathogen-associated molecular pattern (PAMP) signal as seen in the case of virus-like particle (VLP), allowing the immune system to mount an effective immune response. We have developed a unique self-assembling nanoparticle-based vaccine platform that is amenable to the display of trimeric proteins (e.g. influenza virus hemagglutinin (HA) or other viral spike proteins) and monomeric proteins (e.g. receptor-binding domain or other antigenic domains/epitopes) in a rigidly repetitive manner. These immunogens elicit robust host immune responses when immunized compared to the parental monomer or trimeric molecules. Furthermore, alteration of accessibility and/or orientation of antigens on a nanoparticle enables focusing of the immune response to specific epitopes that can be difficult to target using traditional vaccines. More recently, we created a system to display antigenically heterogeneous influenza HA receptor-binding domains (RBDs) on a single self-assembling nanoparticle to co-localize diverse antigens at a single cell level and selectively stimulate cross-reactive (multi-specific) B cells. Immunization with the co-assembled RBD-nanoparticles resulted in broader antibody responses compared to a cocktail mixture or sequential immunization encompassing the same set of RBDs displayed individually. This non-natural antigen array may represent a potential pathway to preferentially induce cross-reactive B cell responses that can lead to a more efficacious vaccine against ever-changing influenza and other viruses that evade the host immune response by antigenic diversity. In sum, self-assembling nanoparticles are a powerful platform to design immunogens that present antigens in either a natural or a non-natural array, and elicit robust immune responses to a variety of pathogens and potentially to self-antigens if desired.