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.
Highlights
IntroductionVaccination is the most effective strategy to prevent or limit the severity of infectionassociated syndromes by training the immune system to recognize and destroy the invading pathogens [1]
In the first step (i), the cholesterol was modified by Glycine-Boc using
Steglish esterification to generate Boc-Gly cholesterol, and (ii) the Boc group was removed by TFA/DCM
Summary
Vaccination is the most effective strategy to prevent or limit the severity of infectionassociated syndromes by training the immune system to recognize and destroy the invading pathogens [1]. New-generation vaccine candidates usually employ a highly purified sub-portion of the pathogen as an antigen; these components often lack immunogenicity, necessitating adjuvants to facilitate the induction of adaptive immunity [2]. The most common salts for large-scale vaccination are aluminum-based mineral salts that mainly function as a depot to drive humoral immunity; they are usually limited by the weak stimulation of cell-mediated immunity [3,4].
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