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- Title
Hyaluronic Acid-Glycine-Cholesterol Conjugate-Based Nanoemulsion as a Potent Vaccine Adjuvant for T Cell-Mediated Immunity.
- 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
- Abstract
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.
- Subjects
CYTOTOXIC T cells; CELLULAR immunity; LABORATORY mice; INTRAMUSCULAR injections; DRUG utilization; HYALURONIC acid
- Publication
Pharmaceutics, 2021, Vol 13, Issue 10, p1569
- ISSN
1999-4923
- Publication type
Article
- DOI
10.3390/pharmaceutics13101569