Experimental and Computational Observations of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association
| Autor: | Xuedan He, Conrard Giresse Tetsassi Feugmo, Jonathan F. Lovell, Mikko Karttunen, Joaquin Ortega, Kazutoyo Miura, Aida Razi, Jasmin Federizon, Wei-Chiao Huang |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Biophysics
malaria Phospholipid Pharmaceutical Science lcsh:RS1-441 02 engineering and technology Article lcsh:Pharmacy and materia medica 03 medical and health sciences chemistry.chemical_compound Antigen antigens Lipid bilayer 030304 developmental biology particles 0303 health sciences Liposome Bilayer Corrin food and beverages vaccines 021001 nanoscience & nanotechnology Lipids Small molecule Porphyrin molecular dynamics Chemistry chemistry simulations 0210 nano-technology bilayers |
| Zdroj: | Pharmaceutics, Vol 13, Iss 98, p 98 (2021) Pharmaceutics Chemistry Publications Volume 13 Issue 1 |
| ISSN: | 1999-4923 |
| Popis: | Cobalt porphyrin phospholipid (CoPoP) can incorporate within bilayers to enable non-covalent surface-display of antigens on liposomes by mixing with proteins bearing a polyhistidine tag (his-tag) however, the mechanisms for how this occurs are poorly understood. These were investigated using the his-tagged model antigen Pfs25, a protein antigen candidate for malaria transmission-blocking vaccines. Pfs25 was found to associate with the small molecule aquocobalamin, a form of vitamin B12 and a cobalt-containing corrin macrocycle, but without particle formation, enabling comparative assessment. Relative to CoPoP liposomes, binding and serum stability studies indicated a weaker association of Pfs25 to aquocobalamin or cobalt nitrilotriacetic acid (Co-NTA) liposomes, which have cobalt displayed in the aqueous phase on lipid headgroups. Antigen internalization by macrophages was enhanced with Pfs25 bound to CoPoP liposomes. Immunization in mice with Pfs25 bound to CoPoP liposomes elicited antibodies that recognized ookinetes and showed transmission-reducing activity. To explore the physical mechanisms involved, we employed molecular dynamics (MD) simulations of bilayers containing phospholipid, cholesterol, as well as either CoPoP or NTA-functionalized lipids. The results show that the CoPoP-containing bilayer creates nanodomains that allow access for a limited but sufficient amount of water molecules that could be replaced by his-tags due to their favorable free energy properties allowing for stabilization. The position of the metal center within the NTA liposomes was much more exposed to the aqueous environment, which could explain its limited capacity for stabilizing Pfs25. This study illustrates the impact of CoPoP-induced antigen particleization in enhancing vaccine efficacy, and provides molecular insights into the CoPoP bilayer properties that enable this. |
| Databáze: | OpenAIRE |
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