Cholic Acid-based Delivery System for Vaccine Candidates against Group A Streptococcus
Author(s)
Azuar, Armira
Zhao, Lili
Hei, Tsui Ting
Nevagi, Reshma J
Bartlett, Stacey
Hussein, Waleed M
Khalil, Zeinab G
Capon, Robert J
Toth, Istvan
Skwarczynski, Mariusz
Griffith University Author(s)
Year published
2019
Metadata
Show full item recordAbstract
Peptide-based subunit vaccines require an immunostimulant (adjuvant) and/or delivery system to protect the antigenic peptide from degradation and induce the desired immunity. Currently available adjuvants are either too toxic for human use (experimental adjuvants) or they are limited for use in particular vaccines or licensed countries (commercial adjuvants). Therefore, there is an immediate need for novel adjuvants that are both safe and effective. Herein, we assessed the ability of cholic acid (a major bile acid) as a nontoxic, biodegradable, human-derived, potent vaccine delivery system. An antigenic peptide derived from ...
View more >Peptide-based subunit vaccines require an immunostimulant (adjuvant) and/or delivery system to protect the antigenic peptide from degradation and induce the desired immunity. Currently available adjuvants are either too toxic for human use (experimental adjuvants) or they are limited for use in particular vaccines or licensed countries (commercial adjuvants). Therefore, there is an immediate need for novel adjuvants that are both safe and effective. Herein, we assessed the ability of cholic acid (a major bile acid) as a nontoxic, biodegradable, human-derived, potent vaccine delivery system. An antigenic peptide derived from Group A Streptococcus was conjugated to hydrophobic cholic acid via solid phase peptide synthesis to produce lipopeptide that self-assembled into rod-like nanoparticles under aqueous conditions. Following intranasal immunization in mice, this lipopeptide was capable of inducing the production of opsonic epitope-specific antibodies on its own and in liposomal formulation. The cholic acid-based conjugate induced significantly stronger humoral immune responses than cholera toxin-based adjuvant. Thus, we demonstrated, for the first time, capability of the human-derived lipid to act as a built-in immunoadjuvant for vaccines.
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View more >Peptide-based subunit vaccines require an immunostimulant (adjuvant) and/or delivery system to protect the antigenic peptide from degradation and induce the desired immunity. Currently available adjuvants are either too toxic for human use (experimental adjuvants) or they are limited for use in particular vaccines or licensed countries (commercial adjuvants). Therefore, there is an immediate need for novel adjuvants that are both safe and effective. Herein, we assessed the ability of cholic acid (a major bile acid) as a nontoxic, biodegradable, human-derived, potent vaccine delivery system. An antigenic peptide derived from Group A Streptococcus was conjugated to hydrophobic cholic acid via solid phase peptide synthesis to produce lipopeptide that self-assembled into rod-like nanoparticles under aqueous conditions. Following intranasal immunization in mice, this lipopeptide was capable of inducing the production of opsonic epitope-specific antibodies on its own and in liposomal formulation. The cholic acid-based conjugate induced significantly stronger humoral immune responses than cholera toxin-based adjuvant. Thus, we demonstrated, for the first time, capability of the human-derived lipid to act as a built-in immunoadjuvant for vaccines.
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Journal Title
ACS Medicinal Chemistry Letters
Volume
10
Issue
9
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Pharmacology and pharmaceutical sciences