Experimental and Computational Observations of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association

Jasmin Federizon; Conrard Giresse Tetsassi Feugmo; Wei-Chiao Huang; Xuedan He; Kazutoyo Miura; Aida Razi; Joaquin Ortega; Mikko Karttunen; Jonathan F. Lovell

doi:10.3390/pharmaceutics13010098

Pharmaceutics (Jan 2021)

Experimental and Computational Observations of Immunogenic Cobalt Porphyrin Lipid Bilayers: Nanodomain-Enhanced Antigen Association

Jasmin Federizon,
Conrard Giresse Tetsassi Feugmo,
Wei-Chiao Huang,
Xuedan He,
Kazutoyo Miura,
Aida Razi,
Joaquin Ortega,
Mikko Karttunen,
Jonathan F. Lovell

Affiliations

Jasmin Federizon: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
Conrard Giresse Tetsassi Feugmo: Department of Chemistry, the University of Western Ontario, London, ON N6A 3K7, Canada
Wei-Chiao Huang: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
Xuedan He: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA
Kazutoyo Miura: Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
Aida Razi: Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada
Joaquin Ortega: Department of Anatomy and Cell Biology, McGill University, Montreal, QC H3A 0C7, Canada
Mikko Karttunen: Department of Chemistry, the University of Western Ontario, London, ON N6A 3K7, Canada
Jonathan F. Lovell: Department of Biomedical Engineering, University at Buffalo, State University of New York, Buffalo, NY 14260, USA

DOI: https://doi.org/10.3390/pharmaceutics13010098
Journal volume & issue: Vol. 13, no. 1
p. 98

Abstract

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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.

Published in Pharmaceutics

ISSN: 1999-4923 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceutics/

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