Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity

Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ing...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutics 2021-09, Vol.13 (10), p.1569
Main Authors: Lin, Chih-An, Ho, Hui-Min, Venkatesan, Parthiban, Huang, Chiung-Yi, Cheng, Yu-Jhen, Lin, Yu-Hsing, Lin, Hua-Yang, Chen, Tzu-Yang, Huang, Ming-Hsi, Lai, Ping-Shan
Format: Article
Language:English
Subjects:
Antigens
Aqueous solutions
Biocompatibility
Cholesterol
Chromatography
Coronaviruses
COVID-19 vaccines
Hyaluronic acid
Molecular weight
nanoemulsion
Nanoemulsions
PEG-free formulation
Polyethylene glycol
Spectrum analysis
squalene
vaccine adjuvants
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Clinical cases of allergic reaction that are due to excipients containing polyethylene glycol (PEG), a hydrophilic molecule commonly used in drug/vaccine formulations, has attracted much attention in recent years. In order to develop PEG-free adjuvants, we investigated the feasibility of natural ingredients in the human body such as hyaluronic acid in the form of hyaluronic acid-glycine cholesterol (HACH) conjugate as an excipient for vaccine formulation. Interestingly, HACH grafted with ~13 wt.% cholesterol has good water dispersity and can serve as an emulsifier to stabilize the squalene/water interfaces, yielding a milky white and isotropic emulsion (SQ@HACH) after being passed through a high-shear microfluidizer. Our results show that SQ@HACH particles possessed a unimodal average hydrodynamic diameter of approximately 190 nm measured by dynamic light scattering and exhibited good stability upon storage at 4 °C and 37 °C for over 20 weeks. The results of immunogenicity using a mouse model with ovalbumin (OVA) as the antigen revealed that SQ@HACH significantly enhanced antigen-specific immune responses, including the polarization of IgG antibodies, the cytokine secretions of T cells, and enhancement of cytotoxic T lymphocyte (CTL) activation. Moreover, SQ@HACH revealed lower local inflammation and rapidly absorbing properties compared with AlPO4 after intramuscular injection in vivo, indicating the potential functions of the HA-derived conjugate as an excipient in vaccine formulations for enhancement of T cell-mediated immunity.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics13101569